Development of a Novel Bivalent Vaccine Candidate against Hepatitis A Virus and Rotavirus Using Reverse Vaccinology and Immunoinformatics | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Development of a Novel Bivalent Vaccine Candidate against Hepatitis A Virus and Rotavirus Using Reverse Vaccinology and Immunoinformatics Hassan Yarmohammadi, Abbas Akhavan Sepahi, Mojtaba Hamidi-fard, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3952800/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Hepatitis A virus (HAV) and rotavirus are mainly transmitted through fecal-oral and person-to-person contact, which cause severe gastrointestinal complications and liver diseases. This work used reverse vaccinology and immunoinformatic methods to create a novel bivalent vaccination against the rotavirus and HAV. The amino acid sequences of HAV-rotavirus proteins (VP1 and VP8*) were retrieved from GenBank. Multi-epitope DNA structures. Various computational approaches were employed to predict highly conserved regions and the most immunogenic B-cell and T-cell epitopes of VP8 and VP1 of rotavirus and HAV proteins in both humans and BALB/c. Moreover, the predicted fusion protein was analyzed regarding primary and secondary structures and homology validation. In this study, we used two highly conserved peptide sequences of VP8 and VP1 of rotavirus and HAV that induce T and B cell immunogenicity. According to T-cell epitope prediction, this area comprises 2713 antigenic peptides for HLA class II and 30 HLA class I antigenic peptides, both of which are virtually entirely conserved in the Iranian population. In this study, validation as well as analysis of the secondary and three-dimensional structure of the VP8*-rotavirus + AAY + HAV-VP1 fusion protein, with the aim of designing a multi-epitope vaccine with different receptors such as complications. TLR), 3,4 high immunogenic binding ability with immunological properties and interaction between multi-epitope target and TLR receptors were predicted, and it is expected that the target protein fusion has stable antigenic potency and compatible half-life. The above is suggested as universal vaccination programs. Recombinant Vaccine Immunoinformatic Rotavirus Hepatitis A Virus Bivalent Vaccine Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Various human viruses can multiply in the digestive system and the most common way of their transmission is through the fecal-oral route, water and food contamination, as well as a result of the indiscriminate discharge and leakage of sewage in the living environment and their non-treatment, high-risk human behaviors such as abandoning Feces of sick people in the play area and the work environment, which can contaminate the running water and even penetrate into tap water sources, are among the factors of the spread of intestinal viruses. and facilitate the cycle of further transmission of the disease to vulnerable people. The most common viruses that are spread in this way are rotaviruses and HAV, which are responsible for acute hepatitis and gastroenteritis, respectively( 1 , 2 ). HAV, a member of the Hepatovirus genus causing a self-limiting illness, belongs to the Picornaviridae family. The World Health Organization (WHO) estimates that yearly there are About 30,000 and 35,000 fatalities and 100 million HAV infections. Several nations in the Middle East and Northern Africa (MENA) area, including Iran, have high or extremely high HAV endemicity levels. Recent research indicates that during the past few decades, the frequency of HAV infection in Iran has dramatically reduced. However, the virus is still widespread in some portions of the nation, notably in border regions and rural areas with poor sanitation. Adults with lower socioeconomic level have higher immunogenicity and more asymptomatic HAV infection, and vice versa ( 1 ) . The Reoviridae family of viruses, which includes rotaviruses, is divided into seven groups (A-G). In underdeveloped nations in Africa, Asia, and Latin America, it is estimated that there are 744 million to 1 billion cases of diarrhea and 2.4 million to 3.3 million fatalities among children under the age of five per year. This equates to 6,600 to 9,000 deaths every day. The most common cause of severe gastroenteritis in children under five years of age in developing and industrialized and less developed countries are rotaviruses ( 3 ). HAV and Rotavirus vaccinations are now accessible. There are presently two approved oral rotavirus vaccinations on the market ( 2 , 4 ): RotaTeq® from Merck ( 5 ) and Rotarix® from GlaxoSmithKline ( 6 ). In contrast, there are three approved HAV vaccines, including the inactivated combination vaccination Twinrix and the single-antigen vaccines Havrix and Vaqta ( 7 , 8 ). The safety and effectiveness of all three vaccinations, which are created from inactivated HAV, are equivalent. The use of these vaccinations is presently authorized in the US. Although vaccinations against these viruses have been produced, not all people, especially in low-income countries, have access to them ( 9 ). This emphasizes how urgently more work has to be done to guarantee that vaccinations are available and inexpensive for all populations, regardless of their financial situation ( 5 , 10 , 11 ) . The VP1, VP2, VP3, and VP4 capsid proteins are all present in 60 copies in the capsid of the hepatitis A virus (HAV) ( 12 ). The interaction between the exterior surface of the constructed capsid and a receptor on the surface of the host cell is necessary for the virus to enter the cell. The capsid surface also interacts with the host's antibodies, which may be able to neutralize the virus and stop infection. 42 antigenic areas of the HAV polyprotein were discovered using peptide mapping in earlier investigations ( 13 ). Numerous investigations have demonstrated that VP1 stimulates the development of antibodies that are neutralizing ( 14 ). As a result, it is thought that the VP1 protein may be a candidate for a recombinant vaccination ( 15 ). Rotavirus, on the other hand, has a segmented genome that codes for six structural and six nonstructural proteins ( 16 ). The outer surfaces of the virions include the two key structural proteins VP4 and VP7 ( 17 ). By way of proteolytic cleavage, VP4 is split into two subunits, VP5 and VP8 ( 18 , 19 ). It is thought that VP8* plays a key role in viral attachment to host cells ( 20 – 22 ). The study of peptide-based vaccinations has grown in popularity. Long peptides with immunodominant epitopes may be employed as vaccines if they can stimulate both humoral and cellular immunity against a variety of serological types ( 23 , 24 ). The terms "multivalent" and "multivalent vaccine" are frequently used imprecisely to refer to two distinct vaccine types ( 25 ): one that may provide protection against numerous illnesses with a single vaccine and one that can provide protection against multiple strains of a single pathogen ( 25 – 27 ). Because they can protect against several illnesses with fewer injections, lower the cost of healthcare and patient care, and streamline vaccination programs while preserving the effectiveness and safety of single-component vaccines, efficient multivalent vaccines are highly desired ( 28 , 29 ). It is vitally necessary to develop a multivalent peptide-based vaccination against HAV and rotavirus, especially in low-income nations where the illness burden is high and access to clean water and healthcare is constrained ( 30 , 31 ). Bioinformatics tools of multi-domain analysis, essential estimation in fusion protein production to elucidate immunologically conserved residues, lead to the emergence of new disciplines in the field of immunoinformatics-based multi-epitope vaccine design and construction ( 32 ), such as epitope prediction, efficacy analysis, safety, it provides the effects of toxicity without the need for the growth of pathogenic agents and thus accelerates the vaccine development process ( 25 , 33 ). The goal of this work is to create a new, recombinant VP8*-rotavirus + AAY + HAV-VP1 fusion protein utilizing a flexible linker with a proteasome-cleavable site. This protein combines VP4 (VP8*) with the immunodominant portions of VP1. This strategy is to develop a bivalent vaccination candidate that may concurrently protect against rotavirus and the hepatitis A virus. Success of such a vaccine would depend to a large extent on the antigenic peptide to be used in antibody production. The non-glycosylated protein VP4 on the surface capsid of the virus is important in Rota viral immunogenicity and the major antigenic site(s) responsible for neutralization of the virus via VP4 is in the VP8* subunit of VP4. It is necessary that the peptide should be very specific and a peptide sequence which would stimulate both the T and B immunogenic cells would provide maximum protection against the virus. Advanced computational techniques and existing databases of sequences of the VP4 protein of rotavirus help in identification of such specific sequences. Using an Insilco approach, we have identified a highly conserved VP8* subunit of the VP4 surface protein of rotavirus which shows both T and B cell processivity and is also non-allergenic. This sub-unit could be used in in vivo models for induction of antibodies( 19 ) G1P[8] rotavirus strain As the dominant strain responsible for the spread of rotavirus infection in Iran and other parts of the world, we consider it in this study. MATERIAL AND METHODS 2.1. Amino Acid Sequence Retrieval The VP1-HAV (NP_740552.1), VP8* rotavirus G1P[8] (NCBI accession number:ALU63988.1), CAC14074.3 (IIIA), AAU87586.1 (IIA), BAF37541.1 (IIIB), AAK44219.2 (IIB), and AF314208.1 (IB) sequences were obtained in FASTA format from GenBank of the National Centre for Biotechnology Information (NCBI)( 34 ). 2.2. Determination of Conserved Regions The obtained sequences were aligned using MEGA6.0 ClustalW and the multiple sequence alignment (MSA) program to determine the degree of conservation. Using the Bio edit tool, MSA was visualized ( 35 , 36 ). 2.3. Prediction of T-cell Epitopes in BALB/c and Human We used a combined peptide library to evaluate and evaluate matrices (Comblib Sidney2008) and submitted the acquired sequences to the IEDB's MHCI- and MHCII-binding prediction tool ( http://tools.iedb.org/mhc/n ) using a variety of techniques, including artificial neural networks (ANN), stabilized matrix methods (SMM), and SMM. Additionally incorporated were Rank PEP server and MHC-NP net CTLpan1.1 server. Results from all employed procedures all came within a similar range. T-cell epitope lengths were set at 9 mers for MHC class I and 15 mers for MHC class II for BALB/c and human, respectively. The MHC class I alleles for BALB/c were H2-Dd, H2-Kd, and H2-Ld, whereas the MHC class II alleles were H2-IAd and H2-IEd. Based on the diversity of antigens and the level of identification by the variable HLA molecules in a population, as well as the most prevalent HLA in the Persian population based on the available report, HLA-A*01, 02, 03, 11, 24, 26, 32, HLA-B*35, 51, 50, 27, 57, and HLA-DRB1*15, 11, 13, 03, 04, 07 were selected for MHC class I and MHC class II, respectively. 2.4. Predictions of Antigenicity, Immunogenicity, Population Coverage, and Epitope Conservancy The antigenicity scores of discovered epitopes were assessed using the online VaxiJen v2.0 antigen prediction programme ( 37 , 38 ), which enables the arrangement of antigens according to the physicochemical properties of the protein without the need for sequence alignment. Antigenic scores greater than 0.5 4 were used to define such epitopes. Through the IEDB tool in the Iranian population ( http://tools.iedb.org/population/ ), the predicted peptides interacting with MHC I and II molecules in the considered area were investigated ( 39 ). 2–5. Toxicity and Allergenicity Analyses We evaluated the toxicity of the selected model using ToxinPred ( 40 ). This tool may be used to check all physicochemical properties to confirm that epitopes are safe for the host. The allergenicity was examined using AllerTOP v.2.0 ( 41 ). 2–6. Prediction of linear and Conformational B-cell Epitopes The BepiPred ( 42 ) linear epitope prediction service from the Immune Epitope Database was used to forecast linear B cell epitopes with a threshold of 0.35 and lengths ranging from 6 to higher residues. The approaches for identifying various physicochemical characteristics of amino acids, such as antigenicity, surface accessibility, flexibility, hydrophilicity, and beta-turns, were also evaluated using the tools of the Immune Epitope Database (IEDB) Analysis Resource ( http://tools.iedb.org/bcell ) platform. The protein sequence scanning window was extended in all approaches to 389 residues. With a minimum score of 0.50, we utilized the IEDB online programme ElliPro to predict discontinuous B-cell epitopes. This technique predicts epitopes by taking into account both structure- and sequence-based information. 2.7. Primary and secondary Structure Assessment The physicochemical characteristics of the fragments, including their weight, aliphatic index, Grand average of hydropathicity (GRAVY), theoretical pI, and atomic composition, were examined using Expasy's ProtParam service. The self-optimized prediction method with alignment (SOPMA) and Jpred tools were used to assess the secondary structure of the proteins' a-helix, b sheets, and random coils ( 43 ). 2.8. Homology Modeling and Validation The Threading ASSEmbly Refinement (I-TASSER) online server programmes were developed by Zhang Y. (2008). Protein 3D Structure Prediction I-Tasser Server. IntFOLD Integrated Protein Structure and Function Prediction Server ( 41 ), which provides 3D models as well as a confidence score (C-Score) and a model quality score, was used in the analysis of the 3D models (BMC Bioinformatics). Then, an analysis of the three DFIRE2 indicators—energy profile, C-score, and stereochemical qualities—was conducted ( 40 , 44 ). Utilizing the GalaxyRefine server ( http://galaxy.seoklab.org/ ), the projected vaccine build model will be improved and refined( 45 ). The ProSA-web server was used to evaluate the three-dimensional model ( 46 ) ( https://prosa.services.came.sbg.ac.at/prosa.php ). Additionally, the Ramachandran graph of the three-dimensional structure was created using the MolProbity service ( http://molprobity.biochem.duke.edu/ ) ( 47 ). 2.9. Molecular Docking Analysis To activate innate immune cells in antiviral responses, Toll-like receptors (TLRs) are used as integral membrane proteins on innate immune effector cells. TLR3 and TLR4 can recognize structural glycoproteins and specific forms of viral nucleic acids and nonstructural proteins, leading to the release of inflammatory cytokines, and are important in recognizing viral genetic material in end lysosomal compartments to initiate antiviral responses ( 48 ). To understand the interaction between their structure and TLRs, we obtained the crystal structures of TLR3 and TLR4 from the Protein Data Bank using PDB IDs 3FXI and 1Z1W. Subsequently, we used the ClusPro 2.0 server, which is based on the PIPER Fast Fourier Transform (FFT) correlation method, to bind TLR3 and TLR4 to vaccine protein as ligands for binary interaction. The docking process obtained 30 models through three sequential steps: rigid-body docking, cluster-preserving structures, and refinement using CHARMM minimization. The best cluster was selected based on the lowest score. Finally, PyMOL was used to visualize binding structures and evaluate interactions between TLRs and vaccines ( 49 , 50 ). RESULTS The Iranian population's highly preserved VP8*-rotavirus + AAY + HAV-VP1 fusion protein areas were chosen. The variable sections were removed in order to produce the most appropriate shortened version of HAV, and as a result, amino acids 99 to 259 in the VP1 alignment comprised the most conserved amino acids throughout the clades. Additionally, the viral VP8* amino acids 68 to 277 were used. This study led to the selection of VP8*-rotavirus + AAY + HAV-VP1 fusion protein for further evaluation. 3.1. MHC Class I and II Binding Prediction in BALB/c and Human To design a more efficient and high-throughput vaccination model, we looked at the 9 m coverage of T-cell epitopes in BALB/c. (Table 1 ). According to the IEDB recommendations, the MHC-NP, net CTLpan1.1, RANKPEP, and netMHCpan3.0 servers were utilized to anticipate the potential epitopes. T-cell epitopes were evaluated using a variety of methods to improve prediction precision. High affinity peptides with the antigenic characteristic (percentile rank 1) are indicated as a result of the findings in Table 1 . Accordingly, of the 42 MHC class I epitopes in our construct, 29 were found to be antigenic in BALB/c, and for MHCII, 6 epitopes were predicted (percentile rank 1), of which WTAVVAIEPHVNPVD, IHSEFYIIPRSQESK, and TAVVAIEPHVNPVDR were antigenic epitopes. Allele Peptide Start End Percentile rank Antigenicity H-2-Ld LPSTLRWFF 252 260 0.02 0.37 H-2-Dd RGPLDLTII 267 275 0.02 1.20 H-2-Kd NYNHSDEYL 364 372 0.07 0.47 H-2-Kd EYLSFSCYL 370 378 0.01 1.53 H-2-Dd HGLPSTLRW 250 258 0.11 0.42 H-2-Dd FTPPNDYWI 7 15 0.13 0.05 H-2-Dd ISITIHSEF 129 137 0.16 1.26 H-2-Ld PPHGLPSTL 248 256 0.17 0.02 H-2-Ld GPLDLTIII 268 276 0.19 1.54 H-2-Dd RNDSNKWKF 64 72 0.25 1.04 H-2-Kd RWFFNLFQL 257 265 0.29 0.33 H-2-Kd KYGGRVWTF 101 109 0.32 0.23 H-2-Ld NPVDRQYTI 46 54 0.36 0.93 H-2-Ld ISITIHSEF 129 137 0.37 1.26 H-2-Dd STSNPPHGL 244 252 0.37 0.22 H-2-Dd TPPNDYWIL 8 16 0.4 0.04 H-2-Dd SNKWKFLEM 67 75 0.43 0.67 H-2-Ld TPPNDYWIL 8 16 0.47 0.04 H-2-Dd KEYTFPITL 234 242 0.47 1.29 H-2-Dd STLRWFFNL 254 262 0.51 0.71 H-2-Dd TSDTRLVGI 91 99 0.51 0.78 H-2-Dd NSNNKEYTF 230 238 0.56 0.97 H-2-Dd RTGNIQIRL 323 331 0.57 1.84 H-2-Ld MAWFTPVGL 285 293 0.6 1.31 H-2-Ld KEYTFPITL 234 242 0.6 1.29 H-2-Kd SYLYAVSGA 335 343 0.62 0.39 H-2-Kd KFGNSIVKM 208 216 0.63 0.09 H-2-Kd KEYTFPITL 234 242 0.63 1.23 H-2-Dd IIVSKTSLW 186 194 0.64 0.52 H-2-Dd VGLAVDTPW 291 299 0.7 0.53 H-2-Dd YNRDIIIRF 199 207 0.72 0.39 H-2-Kd IRLPWYSYL 329 337 0.75 0.71 H-2-Kd TFGLVSIQI 354 362 0.79 2.09 H-2-Dd LSIDYKTAL 306 314 0.8 1.47 H-2-Dd KTALGAVRF 311 319 0.83 0.89 H-2-Kd WFTPVGLAV 287 295 0.84 1.40 H-2-Dd SSTANLNNI 121 129 0.84 0.68 H-2-Dd RTLTSDTRL 88 96 0.88 0.21 H-2-Kd IRFKFGNSI 205 213 0.92 1.14 H-2-Kd YRGPLDLTI 266 274 0.93 1.01 H-2-Ld LPWYSYLYA 331 339 0.96 0.35 H-2-Kd RFKFGNSIV 206 214 0.98 0.46 *Antigenicity scores ≥ 0.4 are shown in bold Table 1. In silico analysis of predicted BALB/c MHC class Ι. Allele Peptide Start End Percentile rank Toxicity Antigenicity Allergenicity HLA-A*02:06 AIEPHVNPV 40 48 0.21 Non-Toxin 1.0847 Non-Allergen HLA-A*02:01 0.45 HLA-A*01:01 ANYNHSDEY 363 371 0.6 Non-Toxin 0.5623 Non-Allergen HLA-A*26:01 0.85 HLA-A*02:06 AVVAIEPHV 37 45 0.08 Non-Toxin 0.7941 Non-Allergen HLA-A*02:01 0.33 HLA-A*26:01 DIIVSKTSL 185 193 0.5 Non-Toxin 0.8737 Non-Allergen HLA-B*35:03 0.58 HLA-B*51:01 DSTFGLVSI 352 360 0.26 Non-Toxin 1.9570 Non-Allergen HLA-A*11:01 ESALSIDYK 303 311 0.88 Non-Toxin 1.8557 Non-Allergen HLA-A*24:02 EYLSFSCYL 370 378 0.27 Non-Toxin 1.5388 Non-Allergen HLA-B*51:01 GPLDLTIII 268 276 0.21 Non-Toxin 1.5477 Non-Allergen HLA-B*35:03 0.31 HLA-B*57:01 HGLPSTLRW 250 258 0.02 Non-Toxin 0.4250 Non-Allergen HLA-B*50:01 IDYKTALGA 308 316 0.59 Non-Toxin 1.3147 Non-Allergen HLA-A*32:01 186 194 0.06 Non-Toxin 0.5202 Non-Allergen HLA-B*57:01 IIVSKTSLW 0.12 HLA-A*26:01 0.82 HLA-A*24:02 1 HLA-B*27:02 IRFKFGNSI 205 213 0.14 Non-Toxin 1.1449 Non-Allergen HLA-A*32:01 KTALGAVRF 311 319 0.03 Non-Toxin 0.8993 Non-Allergen HLA-B*57:01 0.13 HLA-A*24:02 0.82 HLA-A*01:01 KTDSTFGLV 350 358 0.5 Non-Toxin 1.6797 Non-Allergen HLA-A*02:06 0.94 HLA-B*35:01 LGDKTDSTF 347 355 0.94 Non-Toxin 1.3270 Non-Allergen HLA-A*11:01 LSSRSIQYK 170 178 0.18 Non-Toxin 1.1724 Non-Allergen HLA-A*03:01 0.41 HLA-A*26:01 357 365 0.17 Non-Allergen HLA-B*35:01 LVSIQIANY 0.58 Non-Toxin 1.4207 HLA-A*01:01 0.62 HLA-A*02:01 125 133 0.23 Non-Allergen HLA-A*32:01 NLNNISITI 0.53 Non-Toxin 1.7404 HLA-A*02:06 0.7 HLA-B*57:01 230 238 0.64 Non-Toxin 0.9777 Non-Allergen HLA-B*35:01 NSNNKEYTF 0.66 HLA-A*32:01 0.73 HLA-A*26:01 NSNTNGVVY 18 26 0.54 Non-Toxin 0.3576 Non-Allergen HLA-B*51:01 PPIQNTRNV 157 165 0.58 Non-Toxin 1.5373 Non-Allergen HLA-A*32:01 RDIIIRFKF 201 209 0.99 Non-Toxin 1.5910 Non-Allergen HLA-A*32:01 RTGNIQIRL 323 331 0.13 Non-Toxin 1.8437 Non-Allergen HLA-B*57:01 0.56 HLA-A*11:01 SSRSIQYKR 171 179 0.58 Non-Toxin 0.8972 Non-Allergen HLA-B*51:01 TANLNNISI 123 131 0.25 Non-Toxin 1.2061 Non-Allergen HLA-B*35:03 0.37 HLA-B*50:01 TEQSEFYFP 381 389 0.41 Non-Toxin 0.6569 Non-Allergen HLA-A*24:02 TFGLVSIQI 354 362 0.66 Non-Toxin 2.0992 Non-Allergen HLA-B*35:03 TPWVEKESA 297 305 0.6 Non-Toxin 0.4216 Non-Allergen HLA-B*35:01 0.95 HLA-B*50:01 VEKESALSI 300 308 0.08 Non-Toxin 1.0647 Non-Allergen HLA-A*02:06 YINNGLPPI 151 159 0.11 Non-Toxin 0.9097 Non-Allergen HLA-A*02:01 0.18 *Antigenicity scores ≥ 0.4 are shown in bold. Table 2. Predicted MHC class Ι epitopes in human. Using the IEDB MHC prediction tool, the truncated VP8-VP1 protein sequence was compared to human MHC class I and II with well-known HLAs in the Persian population. Tables 2 and 3 illustrate, respectively, the binding peptides for MHC class I (29 epitopes) and II (29 epitopes), some of which interact with several HLAs. Finally, neither the class I nor the class II HLA binders were poisonous nor allergenic. Allele Peptide Start End Percentile rank Toxicity Allergenicity Antigenicity HLA-DRB1*11:53 AYTFNSNNKEYTFPI 226 240 0.58 Non-Toxin NON ALEERHEN 0.88 HLA-DRB1*03:27 CNEYINNGLPPIQNT 148 162 0.6 Non-Toxin NON ALEERHEN 0.64 HLA-DRB1*13:62 DTRLVGILKYGGRVW 93 107 0.84 Non-Toxin NON ALEERHEN 0.14 HLA-DRB1*03:40 EKESALSIDYKTALG 301 315 0.96 Non-Toxin NON ALEERHEN 1.36 HLA-DRB1*03:05 EMQYNRDIIIRFKFG 196 210 0.81 Non-Toxin NON ALEERHEN 0.65 HLA-DRB1*11:17 EPHVNPVDRQYTIFG 42 56 1 Non-Toxin NON ALEERHEN 1.25 HLA-DRB1*03:19 FYNRRTLTSDTRLVG 84 98 0.96 Non-Toxin NON ALEERHEN 0.46 HLA-DRB1*04:66 HSEFYIIPRSQESKC 134 148 0.93 Non-Toxin NON ALEERHEN 0.58 HLA-DRB1*04:89 IQYKRAQVNEDIIVS 175 189 0.5 Non-Toxin NON ALEERHEN 0.42 HLA-DRB1*03:27 KCNEYINNGLPPIQN 147 161 0.83 Non-Toxin NON ALEERHEN 0.63 HLA-DRB1*03:38 KESALSIDYKTALGA 302 316 0.98 Non-Toxin NON ALEERHEN 1.34 HLA-DRB1*07:06 LDLTIIITGATDVDG 270 284 0.52 Non-Toxin NON ALEERHEN 0.61 HLA-DRB1*03:27 NEYINNGLPPIQNTR 149 163 0.58 Non-Toxin NON ALEERHEN 0.98 HLA-DRB1*04:51 NGVVYESTNNSDFWT 22 36 1 Non-Toxin NON ALEERHEN -0.05 HLA-DRB1*04:09 NTNGVVYESTNNSDF 20 34 0.9 Non-Toxin NON ALEERHEN 0.38 HLA-DRB1*07:11 PLDLTIIITGATDVD 269 283 0.98 Non-Toxin NON ALEERHEN 1.2 HLA-DRB1*04:27 RSIQYKRAQVNEDII 173 187 0.99 Non-Toxin NON ALEERHEN 0.14 HLA-DRB1*11:27 SDTRLVGILKYGGRV 92 106 0.99 Non-Toxin NON ALEERHEN 0.44 HLA-DRB1*11:81 SEFYIIPRSQESKCN 135 149 1 Non-Toxin NON ALEERHEN 0.46 HLA-DRB1*13:10 SIQYKRAQVNEDIIV 174 188 1 Non-Toxin NON ALEERHEN 0.46 HLA-DRB1*04:82 SRSIQYKRAQVNEDI 172 186 0.77 Non-Toxin NON ALEERHEN 0.28 HLA-DRB1*04:14 SSQNEFYNRRTLTSD 79 93 0.78 Non-Toxin NON ALEERHEN 0.29 HLA-DRB1*04:87 SSRSIQYKRAQVNED 171 185 0.98 Non-Toxin NON ALEERHEN 0.4 HLA-DRB1*04:07 TNGVVYESTNNSDFW 21 35 1 Non-Toxin NON ALEERHEN 0.14 HLA-DRB1*11:54 TSDTRLVGILKYGGR 91 105 0.9 Non-Toxin NON ALEERHEN 0.49 HLA-DRB1*13:32 VVAIEPHVNPVDRQY 38 52 0.98 Non-Toxin NON ALEERHEN 1.22 HLA-DRB1*04:07 WSAAYTFNSNNKEYT 223 237 0.95 Non-Toxin NON ALEERHEN 0.61 *Antigenicity scores ≥ 0.4 are shown in bold. Table 3 : Predicted MHC class IΙ binders in human B cells produce antibodies as part of humoral immunity. Long-lasting immunity is provided through B-cell receptors' recognition of B-cell epitopes. The ABCpred server discovered 26 epitopes with a score of 0.5 or higher and a length of 16 mer, which the BepiPred tool then verified. Their hydrophilicity, surface accessibility, antigenicity, flexibility, and beta-turn were used to describe them. The mean scores for Emini surface accessibility, Karplus and Schulz flexibility, Parker hydrophilicity, and Kolaskr and tongaonkar antigenicity were determined to be 1.000 (Fig. 1 a), 1.000 (Fig. 1 b), 1.296 (Fig. 1 c), and 1.016 (Fig. 1 e), respectively. At the same time, Chou and Fasman's method was utilized to forecast beta-becomes since beta turns hydrophilic and aids in triggering the immunological response (Rose et al., 1985). The mean, lowest, and highest beta-turn scores were 1.020, 0.641, and 1.407, respectively (Fig. 1 d). The Ellipro server produced six conformational and thirteen linear B-cell epitopes (Tables 4 and 5). PyMOL examined the mapped epitopes. 3.2. Antigenicity, Immunogenicity, Population Coverage, and Epitope Conservancy Analysis An immune-prophylactic vaccine must meet the key requirement of antigenicity. The antigenicity of the suggested vaccine construct was assessed using VaxiJen 2.0 servers to make sure that it would engage with the B and T cell receptors to trigger a sustained immune response. Due to the findings in Tables 1 , 2 , and 3 , high-affinity peptides with the antigenic characteristic (percentile rank 1) are included. Table 5 contains the findings of the overall population coverage in the Persian population. 3.3. Primary and Secondary Structure Analysis The fusion protein with molecular weight and specific model, which is the theoretical isoelectric point, and the hydropathic average - indicating the solubility and hydrophobicity of the desired protein - were calculated using the ProtParam Expasy service. The fusion model has 35 positively charged (Arg + Lys) and 34 negatively charged (Asp + Glu) residues in a polypeptide with a molecular weight of 44.42 kDa and 389 amino acids. This model is also projected to be hydrophilic and dissolvable (GRAVY Great Normal of Hydropathy: -0.397). Using secondary structure analysis and disulfide connections, the SOPMA programme was utilized to predict the secondary structure of Model characteristics such as beta turns, helices, random coil contribution, and C-score. A larger ratio of random coils to extended strands is associated with an increase in the production of protein antigenic epitopes. As a result, 15.17 percent of it is a helix, and 35.48 percent of it is a sheet, which, along with the largest percentage of random coils (42.16) can produce greater antigenic epitopes. Fusion Protein Model predicts the presence of a single disulfide bridge between and that offers stability external to the cell. 3.4. Tertiary Structure Prediction and Validation Model's three-dimensional structure was predicted using the online I-TASSER service, which provides five top models with C-scores ranging from − 5 to 2. The model with the greatest C-score is the most effective one. This value's confidence level was adequate (-1.06) for the model that was chosen. Using PyMOL, the protein picture was produced. Additionally, the Ramachandran plot demonstrated that 271/387, or 70.0%, of all residues, were in favored areas. A total of 338/387 residues, or 87.3%, were in permitted locations (Fig. 2 ). The model's 3D structure had a Z-score of 6.04 (Fig. 3 ). 3.9. Molecular Docking Toll-like receptors (TLRs) are very important for recognizing pathogen-related molecular patterns and regulating the induction of immune responses in viral infections, especially hepatitis A and rotavirus. In this study, out of two Toll-like receptors (TLRs) (4 TLR3,) that TLR3 recognizes viral glycoproteins and lipoproteins and activates immune cells. Activation of TLR4 leads to inflammation and secretion of inflammatory cytokines such as interleukin-6 and 5 through a MyD88-related pathway and also promotes gamma interferon secretion through a MyD88-independent pathway. On the other hand, activation of TLRs-related immune pathways could be therapeutic for hepatitis A rotavirus infections. To evaluate the candidate vaccine binding affinity with TLRs, we used the ClusPro v2.0 binding tool, which is very helpful for evaluating the induction and immune responses. For each TLR binding vaccine design, thirty anchor complexes were generated and the corresponding centers and their lowest energy score was determined. Vaccine/TLR3 and vaccine/TLR4 complexes showed the center score and the lowest energy. The final output with the lowest global energy (-1089) for the vaccine/TLR3 construct and (-1006.8) for our vaccine/TLR4 construct was considered the most favorable interaction. Interactions between vaccine candidates and TLRs were visualized using PyMOL (Fig. 4 ). DISCUSSION Highly infectious viruses like rotavirus and hepatitis A can generate seasonal epidemics and pose a serious risk to the public's health. These viruses are able to easily cross boundaries and infect a variety of organisms. As a result, it is crucial to put in place efficient preventative measures, such vaccinations. Unfortunately, the lack of a bivalent vaccination highlights the necessity for a vaccine or pharmacological intervention to manage these epidemics notwithstanding the high fatality rates and astronomical medical costs associated with these infections ( 22 ). In contrast to traditional vaccination procedures that depend on attenuated or inactivated viral strains, bioinformatics analysis offers a speedier and less complex process for creating recombinant vaccines. The bioinformatics method offers a quicker and more effective technique to find possible vaccine epitopes ( 29 ). In this study, we identified functional epitopes of a fusion protein of rotavirus and hepatitis A viruses (VP8*-rotavirus + AAY + HAV-VP1 fusion protein), including 389 amino acids with high immunogenicity to stimulate T cells and B cells, using advances in bioinformatics tools, the availability of viral genome databases, and previous studies. For rotavirus and hepatitis A, many vaccinations have been investigated. While full-length or truncated VP8* proteins and clinical studies with the p2*- VP8 (two fused VP8* copies) subunit vaccine have also showed promising outcomes, recombinant VP6 proteins have been studied as vaccine candidates for rotavirus. Previous research has examined the effectiveness of Vi-VP8 (comprising many rotavirus groups) combinations in boosting the immune response with a focus on various rotavirus species. According to Mickley et al ., the Vi-VP8 conjugation could induce persistent immunity and had a molecular weight of 49.50 kDa. However, Dormitzer et al . (2002) noted that this strategy may not be successful due to the notable discrepancies between the antigenic epitopes of the VP8* region of rotavirus A strains circulating in different regions of the world. Because the VP8* fragment has more genetic diversity, is more effective against a variety of rotavirus A strains, offers long-term protection from the virus, and also triggers a potent and specific immune response against rotavirus A, we chose to concentrate on it rather than the VP4 fragment. (2012) Zeller et al.( 17 , 19 ). According to earlier research and immunogenicity analyses, long-term booster doses of live, attenuated/inactivated hepatitis A vaccinations resulted in considerable seroconversion and protective protection. However, the sluggish rate of HAV proliferation in cell culture results in low yield, making the manufacture of inactivated vaccines challenging and expensive. In terms of safety, high purity, and well defined structures, recombinant subunit vaccines, which have the capacity to elicit an effective immune response, seem more sensible ( 44 , 51 ). Recombinant proteins can be used to identify particular epitopes, minimize the risk of adverse responses, and examine prospective epitopes in proteins, which provides the possibility of producing vaccines with high ability to fight effectively against diseases caused by viral agents( 33 ) The discovered epitopes in this work have the capacity to trigger humoral immune reactions from memory B cells and to trigger particular immunological reactions against rotavirus and hepatitis A. They can also boost CTL and Th cell activity and produce CTL-mediated responses, which are crucial for controlling viral infection. The promotion of effective CD8 + CTL responses and durable antibody immunological responses through the induction of T-cell-mediated immunity lowers the incidence of illness. Because these epitopes may elicit a potent and focused immune response against rotavirus and hepatitis A, their application in the creation of vaccines holds promise for stopping the spread of these viral diseases ( 31 ). Analysis of the intended structure in revealed the expected epitopes' affinity for mouse MHC-I and II molecules. It was discovered that we have a large number of epitopes with the strongest affinity for binding to mouse MHC-I alleles, and molecular binding study revealed the Mouse alleles with the highest mutual similarity score were H-2-Ld, H-2-Dd, and H-Dd2. The antigenicity of the VP8* region's antigenic epitopes may be impacted by various amino acid variations in their exposed areas. The degree of T cell immunogenicity is significantly influenced by the T cell epitopes' ability to bind to the MHC. Since epitope binding to MHC molecules is necessary for antigen presentation to T cells, it is crucial to find epitopes that interact with MHC I and MHC II polymorphic alleles that have high population coverage scores. Similar research was done on rotavirus from vp7 and vp8, however only three CTL epitopes and four HTL epitopes were found in B cells. This emphasizes the significance of utilizing bioinformatics methods to locate possible vaccine epitopes since they can assist locate certain epitopes that might trigger robust and focused immune responses against viral infections. It is crucial to identify strong epitopes for the rotavirus and hepatitis A viruses in order to create vaccinations that are effective against these viral illnesses. Muhammad Osman as well as others. The strongest epitopes in this investigation were determined to be 9 CTL and HTL epitopes from 389 amino acids with the greatest binding affinities for various MHC molecules and high immunity and protection ratings. For instance, the Pol (215–258) epitope has the maximum binding affinity for five HLA supertypes and 16 common HLA-I alleles. For a number of HLA-B and HLA-A alleles, the epitope also demonstrated strong binding affinity. The secondary and tertiary structures of the vaccine need epitopes connected to the TCR/BCR by the linker sequences AAY and EAAAK. It was discovered that the vaccine's structure comprises of 40% coiled-coil, 42% beta sheets, and 16% alpha helix ( 25 ). The study looked at the physical and chemical characteristics of the vaccine structure, and it was discovered that it had an aliphatic index, a possible hydrophobicity, and a molecular weight of 44.42 kDa. The peptide's total hydropathic average (GRAVY) was 0.381, which designates it as hydrophilic. These traits show that the vaccine protein is thermally stable and appropriate for the rotavirus and hepatitis A vaccines. Alpha helices, extended strands, beta twists, and random helical structures were discovered in the vaccine's secondary and tertiary structures, which were also examined. The Ramachandran diagram's predictions indicated that the three-dimensional structure would have advantageous properties. The vaccine's structural flaws and potential modelling issues were corrected using the ProSA programme, which was also used to determine the structure's overall quality score. The linear epitope prediction was assessed by the amino surface accessibility, Kulascar and Tongaonkar antigenicity test, and Parker hydrophilicity test in order to establish that the vaccine binds to B cells. Epitopes over the threshold were anticipated, and it was discovered that the B cell's surface and epitopes were "hydrophilic". IEDB techniques were used to analyze the target sequence's expected MHC I and II binding to T cells, and it was discovered that T cells are projected to interact with MHC I alleles with an IC 50 = 100.However, the study also discovered that certain amino acid variations occur in the exposed areas of the VP8* region's antigenic epitopes, and these variations may have an impact on antigenicity. Therefore, more research and optimization may be needed to guarantee the vaccine's effectiveness. Assessment, which indicates that this model. The structural analysis of this model revealed that the model that received the highest score (0.994) contained a protein with 389 amino acids and 42.16% random coils. Additionally, the Ramachandran diagram revealed that there were 91.7% non-toxic amino acids in the protein, with a high population coverage, particularly in Iran and Europe. Performance evaluation of protein-protein binding affinity, protein fusion candidate vaccine with mediators of innate immune stimulation actually interacts with rotavirus VP1-HAV ( 52 )and rotavirus, VP8( 53 ) genes with Toll-like receptors (TLRs) for pathogen recognition (eg, TLR3, TLR4) showed that the interaction between the fusion protein can lead to the induction of the release of inflammatory cytokines such as interleukin 6 and 5, as well as promoting the release of gamma interferon and creating an effective innate immune response, which indicates the good performance of the fusion protein as a vaccine candidate against the spread of hepatitis A virus ( 54 ). that the accuracy of the desired study requires experimental and clinical validation. Immunity against diseases is developed by vaccination, which also provides antigenic agents to activate the immune system. On the other hand, immunoinformatic approaches are a very effective tool for designing and studying algorithms to reduce time and cost, as well as the trend of increasing the propagation chain of rotavirus infection and the prevalence of hepatitis A in children. At the moment, there is no effective drug and the time-consuming process of treatment and drug. And the only way to regulate the poor economic conditions in emerging and third-world nations is by offering a possible vaccination. We created a protein fusion as a possible dual vaccination candidate using bioinformatics tools and methodologies ( 26 ). The chosen recombinant protein is next tested in vitro and in vivo to see how strongly it can elicit immunological responses. It may be utilized efficiently to create vaccines quickly and affordably. Although the Insilco results show that the vaccination is efficacious, laboratory testing and animal model studies need be done to evaluate the vaccine's therapeutic efficacy. Additionally, the use of anticipated peptides may result in the creation of native variant DNA vaccines. For in vitro and in vivo investigations, particular attention should be paid to residues that exhibit minimal variability, stimulate B-cell immunity, and have a high affinity to alleles. Additionally, the variety of projected epitopes will rise as a result of the research of molecular epidemiology in many worlds logical systems. As a result, we advise conducting further fieldwork, particularly in nations where there is little knowledge about the rotavirus and hepatitis A strains that are in circulation. It will then be put to use in research. CONCLUSION We designed a fusion protein using bioinformatics tools and methods as a viable recombinant vaccination candidate. Hepatitis A virus VP1 and rotavirus VP8 protein epitopes are present in this vaccination. The chosen recombinant protein can substantially elicit immunological responses and may help in the development of an efficient vaccine to decrease the prevalence of rotavirus and hepatitis A in various populations. Declarations Data Availability declaration: All data supporting the findings of this study are available within the paper and its Supplementary Information. ACKNOWLEDGEMENT The authors thank all of the staffs at Hepatitis and AIDS Dept. of Pasteur Institute of Iran who participated in the study. CONFLICT OF INTERESTS The authors declare that they have no conflict of interests. References Organization WH. WHO immunological basis for immunization series: module 18: hepatitis A. 2019. Damtie D, Melku M, Tessema B, Vlasova AN. Prevalence and genetic diversity of rotaviruses among under-five children in Ethiopia: A systematic review and meta-analysis. Viruses. 2020;12(1):62. Izadi M, Esfahani AA, Hassannia H, Jafari NJ, Najarkolaei FR, Rezaee-Zavareh MS. Seroprevalence of hepatitis A virus among Iranian soldiers. Gastroenterology and hepatology from bed to bench. 2016;9(2):100. Jacobsen KH. Globalization and the changing epidemiology of hepatitis A virus. Cold Spring Harbor Perspectives in Medicine. 2018;8(10). Arıstegui J, Dal-Re R, Dıez-Delgado J, Mares J, Casanovas J, Garcıa-Corbeira P, et al. Comparison of the reactogenicity and immunogenicity of a combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polio (DTPa–HBV–IPV) vaccine, mixed with the Haemophilus influenzae type b (Hib) conjugate vaccine and administered as a single injection, with the DTPa–IPV/Hib and hepatitis B vaccines administered in two simultaneous injections to infants at 2, 4 and 6 months of age. Vaccine. 2003;21(25-26):3593-600. Plosker GL. Rotavirus Vaccine RIX4414 (Rotarix™) A Pharmacoeconomic Review of its Use in the Prevention of Rotavirus Gastroenteritis in Developing Countries. Pharmacoeconomics. 2011;29:989-1009. Ashur Y, Adler R, Rowe M, Shouval D. Comparison of immunogenicity of two hepatitis A vaccines—VAQTA® and HAVRIX®—in young adults. Vaccine. 1999;17(18):2290-6. Wang X, Xu W, Hu Y, Yao H, Xu L, Ma M, et al. Immunogenicity persistence of hepatitis A vaccines Healive® and Havrix® among children: 15 years follow-up and long-term prediction. Human Vaccines & Immunotherapeutics. 2023:2227549. Ott J, Wiersma S. Single-dose administration of inactivated hepatitis A vaccination in the context of hepatitis A vaccine recommendations. International Journal of Infectious Diseases. 2013;17(11):e939-e44. Sagliocca L, Amoroso P, Stroffolini T, Adamo B, Tosti ME, Lettieri G, et al. Efficacy of hepatitis A vaccine in prevention of secondary hepatitis A infection: a randomised trial. The Lancet. 1999;353(9159):1136-9. Amroabadi MA, Rahimi E, Shakerian A, Momtaz H. Incidence of hepatitis A and hepatitis E viruses and norovirus and rotavirus in fish and shrimp samples caught from the Persian Gulf. Arquivo Brasileiro de Medicina Veterinária e Zootecnia. 2021;73:169-78. Nain A, Kumar M, Banerjee M. Oligomers of hepatitis A virus (HAV) capsid protein VP1 generated in a heterologous expression system. Microbial Cell Factories. 2022;21(1):1-12. Peak CM, Stous SS, Healy JM, Hofmeister MG, Lin Y, Ramachandran S, et al. Homelessness and hepatitis A—san diego county, 2016–2018. Clinical infectious diseases. 2020;71(1):14-21. Santos GMCd, Alves CR, Pinto MA, Amado Leon LA, Souza-Silva F. Detection of antibodies against hepatitis A virus (HAV) by a surface plasmon resonance (SPR) biosensor: a new diagnosis tool based on the major HAV capsid protein VP1 (SPR-HAVP1). Sensors. 2021;21(9):3167. DOTZAUER R, VALLBRACHT A, KEIL GM. The proposed gene for VP1 of HAV encodes for a larger protein than that observed in HAV-infected cells and virions. Virology. 1995;213(2):671-5. Hu L, Crawford SE, Hyser JM, Estes MK, Prasad BV. Rotavirus non-structural proteins: structure and function. Current opinion in virology. 2012;2(4):380-8. Li Y, Xue M, Yu L, Luo G, Yang H, Jia L, et al. Expression and characterization of a novel truncated rotavirus VP4 for the development of a recombinant rotavirus vaccine. Vaccine. 2018;36(16):2086-92. Hu L, Crawford SE, Czako R, Cortes-Penfield NW, Smith DF, Le Pendu J, et al. Cell attachment protein VP8* of a human rotavirus specifically interacts with A-type histo-blood group antigen. Nature. 2012;485(7397):256-9. Mohanty E, Dehury B, Satapathy AK, Dwibedi B. Design and testing of a highly conserved human rotavirus VP8* immunogenic peptide with potential for vaccine development. Journal of biotechnology. 2018;281:48-60. Patton JT. Structure and function of the rotavirus RNA-binding proteins. Journal of General Virology. 1995;76(11):2633-44. Kabaabetswe L, Sebunya T, Matsheka M, Ndung'u T. Detection and molecular characterisation of group a rotavirus from children in northern Botswana. East African medical journal. 2005;82(4). Skrobarczyk JW, Martin CL, Bhatia SS, Pillai SD, Berghman LR. Electron-beam inactivation of human rotavirus (HRV) for the production of neutralizing egg yolk antibodies. Frontiers in Immunology. 2022;13:840077. Pavitrakar DV, Atre NM, Tripathy AS, Shil P. Design of a multi-epitope peptide vaccine candidate against chandipura virus: An immuno-informatics study. Journal of Biomolecular Structure and Dynamics. 2022;40(2):648-59. Ismail S, Ahmad S, Azam SS. Immunoinformatics characterization of SARS-CoV-2 spike glycoprotein for prioritization of epitope based multivalent peptide vaccine. Journal of Molecular Liquids. 2020;314:113612. Kuri PR, Goswami P. Current update on rotavirus in-silico multiepitope vaccine design. ACS omega. 2022;8(1):190-207. Usman M, Ayub A, Habib S, Rana MS, Rehman Z, Zohaib A, et al. Vaccinomics Approach for Multi-Epitope Vaccine Design against Group A Rotavirus Using VP4 and VP7 Proteins. Vaccines. 2023;11(4):726. Mosa AI, Urbanowicz RA, AbouHaidar MG, Tavis JE, Ball JK, Feld JJ. A bivalent HCV peptide vaccine elicits pan-genotypic neutralizing antibodies in mice. Vaccine. 2020;38(44):6864-7. Lauer KB, Borrow R, Blanchard TJ. Multivalent and multipathogen viral vector vaccines. Clinical and Vaccine Immunology. 2017;24(1):e00298-16. Dutta K. Multi valent DNA vaccine against group A human rotavirus: an in-silico investigation. BioRxiv. 2020:2020.01. 13.903781. Halsey NA. Safety of combination vaccines: perception versus reality. The Pediatric infectious disease journal. 2001;20(11):S40-S4. Seo DJ, Lee MH, Son NR, Seo S, Lee KB, Wang X, Choi C. Seasonal and regional prevalence of norovirus, hepatitis A virus, hepatitis E virus, and rotavirus in shellfish harvested from South Korea. Food Control. 2014;41:178-84. Ikram A, Alzahrani B, Zaheer T, Sattar S, Rasheed S, Aurangzeb M, Ishaq Y. An in silico deep learning approach to multi-epitope vaccine design: a hepatitis E virus case study. Vaccines. 2023;11(3):710. Rodríguez M, Wood C, Sanchez-López R, Castro-Acosta RM, Ramírez OT, Palomares LA. Understanding internalization of rotavirus VP6 nanotubes by cells: towards a recombinant vaccine. Archives of virology. 2014;159:1005-15. Sayers EW, Cavanaugh M, Clark K, Pruitt KD, Schoch CL, Sherry ST, Karsch-Mizrachi I. GenBank. Nucleic acids research. 2021;49(D1):D92-D6. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: molecular evolutionary genetics analysis version 6.0. Molecular biology and evolution. 2013;30(12):2725-9. Kundu S, Kumar V. Environmental DNA (eDNA) testing for detection of freshwater turtles in Temple pond. Herpetology Notes. 2018;11:369-71. Doytchinova IA, Flower DR. Identifying candidate subunit vaccines using an alignment-independent method based on principal amino acid properties. Vaccine. 2007;25(5):856-66. Doytchinova IA, Flower DR. VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC bioinformatics. 2007;8(1):1-7. Bui H-H, Sidney J, Dinh K, Southwood S, Newman MJ, Sette A. Predicting population coverage of T-cell epitope-based diagnostics and vaccines. BMC bioinformatics. 2006;7(1):1-5. Gupta S, Kapoor P, Chaudhary K, Gautam A, Kumar R, Consortium OSDD, Raghava GP. In silico approach for predicting toxicity of peptides and proteins. PloS one. 2013;8(9):e73957. Oluwaseun FA, Sibuyi NRS, Darius R. Immunoinformatics design of a novel epitope-based vaccine candidate against dengue virus. 2021. Jespersen MC, Peters B, Nielsen M, Marcatili P. BepiPred-2.0: improving sequence-based B-cell epitope prediction using conformational epitopes. Nucleic acids research. 2017;45(W1):W24-W9. Geourjon C, Deleage G. SOPMA: significant improvements in protein secondary structure prediction by consensus prediction from multiple alignments. Bioinformatics. 1995;11(6):681-4. Yang Y, Zhou Y. Specific interactions for ab initio folding of protein terminal regions with secondary structures. Proteins: Structure, Function, and Bioinformatics. 2008;72(2):793-803. Heo L, Park H, Seok C. GalaxyRefine: Protein structure refinement driven by side-chain repacking. Nucleic acids research. 2013;41(W1):W384-W8. Wiederstein M, Sippl MJ. ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic acids research. 2007;35(suppl_2):W407-W10. Chen VB, Arendall WB, Headd JJ, Keedy DA, Immormino RM, Kapral GJ, et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallographica Section D: Biological Crystallography. 2010;66(1):12-21. Lester SN, Li K. Toll-like receptors in antiviral innate immunity. Journal of molecular biology. 2014;426(6):1246-64. Rose PW, Beran B, Bi C, Bluhm WF, Dimitropoulos D, Goodsell DS, et al. The RCSB Protein Data Bank: redesigned web site and web services. Nucleic acids research. 2010;39(suppl_1):D392-D401. Kozakov D, Hall DR, Xia B, Porter KA, Padhorny D, Yueh C, et al. The ClusPro web server for protein–protein docking. Nature protocols. 2017;12(2):255-78. Pollet J, Chen W-H, Strych U. Recombinant protein vaccines, a proven approach against coronavirus pandemics. Advanced drug delivery reviews. 2021;170:71-82. Kashyap P, Deka M, Medhi S, Dutta S, Kashyap K, Kumari N. Association of Toll-like receptor 4 with hepatitis A virus infection in Assam. Acta virologica. 2018;62(1):58-62. Frias AH. Characterization of epithelial responses to rotavirus infection in the gut: Emory University; 2010. Ngoi SM. The opposing immunological effects of double-stranded RNA on cytotoxic CD8 T cell response: University of Connecticut; 2010. Table 4 Table 4 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table4.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3952800","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":274922714,"identity":"ba4c5145-da3c-452b-8ffd-90208593dda4","order_by":0,"name":"Hassan Yarmohammadi","email":"","orcid":"","institution":"Islamic Azad University","correspondingAuthor":false,"prefix":"","firstName":"Hassan","middleName":"","lastName":"Yarmohammadi","suffix":""},{"id":274922715,"identity":"b9ba90a9-7c98-472f-8d97-d613deaa462c","order_by":1,"name":"Abbas Akhavan Sepahi","email":"","orcid":"","institution":"Islamic Azad University","correspondingAuthor":false,"prefix":"","firstName":"Abbas","middleName":"Akhavan","lastName":"Sepahi","suffix":""},{"id":274922716,"identity":"39cd814d-96ea-4ae1-9cf6-47085191ce04","order_by":2,"name":"Mojtaba Hamidi-fard","email":"","orcid":"","institution":"Pasteur Institute of Iran","correspondingAuthor":false,"prefix":"","firstName":"Mojtaba","middleName":"","lastName":"Hamidi-fard","suffix":""},{"id":274922717,"identity":"b6f305f4-3707-42cb-8a45-d746ea2c1805","order_by":3,"name":"Mohammadreza Aghasadeghi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyUlEQVRIiWNgGAWjYNACNiBib2BgJlELzwFStTBIJBCpRXf2AeYPP8psZPsk3xh+LqiwYeBv707Aq8XsXAKbZM+5NOM26Rxj6Rln0hgkzpzdgF/LGaCreNsOJwK1GEgDGQwGErkEtTB//Nv2P7FN8ozxb2K1MAANP5DYJsFjRrQtbNIy55KN23jSyqx5zqTxEOMX5o9vyuxk57cf3nybp8JGjr+9F78WBgb+DyCSsYGBwwDE4CGgHAGAWtgfEK16FIyCUTAKRhYAADRwQRGX6N7sAAAAAElFTkSuQmCC","orcid":"","institution":"Pasteur Institute of Iran","correspondingAuthor":true,"prefix":"","firstName":"Mohammadreza","middleName":"","lastName":"Aghasadeghi","suffix":""},{"id":274922718,"identity":"b3caf801-84f3-49a1-835c-8f0370c8ce12","order_by":4,"name":"Golnaz Bahramali","email":"","orcid":"","institution":"Pasteur Institute of Iran","correspondingAuthor":false,"prefix":"","firstName":"Golnaz","middleName":"","lastName":"Bahramali","suffix":""}],"badges":[],"createdAt":"2024-02-13 06:07:42","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3952800/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3952800/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":51749391,"identity":"0205c618-9013-4cb1-90be-001744ce62d3","added_by":"auto","created_at":"2024-02-28 12:05:45","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":342119,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Emini surface accessibility, (b) Karplus and Schulz flexibility, (c) Parker hydrophilicity, (d) Chou and Fasman beta-turn prediction, and (e) Kolaskr and tongaonkar antigenicity where X- and Y-axis represent the sequence position and respective scores. The line represents the average values of the respective calculated scores and the yellow regions above the average are considered as good.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-3952800/v1/aeb14affd015a597303345e2.png"},{"id":51749392,"identity":"af82fe0f-8639-45a4-9fab-6215f81faf56","added_by":"auto","created_at":"2024-02-28 12:05:46","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":360165,"visible":true,"origin":"","legend":"\u003cp\u003eSequence and structural analysis of Model. (A) Secondary structure by SOPMA tool, (B) Three-dimensional structure by PyMOL red: truncated vp8, yellow: linker and green: truncated vp1. (C) Ramachandran plot of the vaccine structure (70.0% (271/387) of all residues were in favored regions. 87.3% (338/387) of all residues were in allowed regions (http://molprobity.biochem.duke.edu).\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-3952800/v1/3305ca88757441288f48f07f.png"},{"id":51749390,"identity":"aad79af6-fad4-4398-bff0-65d0869dbe9b","added_by":"auto","created_at":"2024-02-28 12:05:45","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":37189,"visible":true,"origin":"","legend":"\u003cp\u003ePROSA validation of 3D vaccine structure showing Z-score (−6.04)\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-3952800/v1/ab54994e176edbcbf1aa044b.png"},{"id":51749397,"identity":"ed0acbb2-3fbd-4b1c-849f-92d240bb6284","added_by":"auto","created_at":"2024-02-28 12:05:47","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":602579,"visible":true,"origin":"","legend":"\u003cp\u003eInteraction between the proposed vaccine construct and TLR3, TLR4, Insilico docking between TLR3, TLR4, and subunit vaccine construct was predicted using ClusPro v2.0 tool; the vaccine construct and the receptor are in red and blue colors, respectively.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-3952800/v1/e8ed0fb6d0796944645640ff.png"},{"id":51848532,"identity":"90f5e6b1-44c4-4307-a1ff-bc568aee5fdf","added_by":"auto","created_at":"2024-03-01 08:05:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1667120,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3952800/v1/103cdb6a-0570-45db-af50-a67c627075dd.pdf"},{"id":51749388,"identity":"4512ed8b-dca5-43ce-9393-a75f593d83b4","added_by":"auto","created_at":"2024-02-28 12:05:44","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":984652,"visible":true,"origin":"","legend":"","description":"","filename":"Table4.docx","url":"https://assets-eu.researchsquare.com/files/rs-3952800/v1/5a708692c8f8da4f377339af.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Development of a Novel Bivalent Vaccine Candidate against Hepatitis A Virus and Rotavirus Using Reverse Vaccinology and Immunoinformatics","fulltext":[{"header":"Introduction","content":"\u003cp\u003eVarious human viruses can multiply in the digestive system and the most common way of their transmission is through the fecal-oral route, water and food contamination, as well as a result of the indiscriminate discharge and leakage of sewage in the living environment and their non-treatment, high-risk human behaviors such as abandoning Feces of sick people in the play area and the work environment, which can contaminate the running water and even penetrate into tap water sources, are among the factors of the spread of intestinal viruses. and facilitate the cycle of further transmission of the disease to vulnerable people. The most common viruses that are spread in this way are rotaviruses and HAV, which are responsible for acute hepatitis and gastroenteritis, respectively(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHAV, a member of the Hepatovirus genus causing a self-limiting illness, belongs to the Picornaviridae family. The World Health Organization (WHO) estimates that yearly there are About 30,000 and 35,000 fatalities and 100\u0026nbsp;million HAV infections. Several nations in the Middle East and Northern Africa (MENA) area, including Iran, have high or extremely high HAV endemicity levels. Recent research indicates that during the past few decades, the frequency of HAV infection in Iran has dramatically reduced. However, the virus is still widespread in some portions of the nation, notably in border regions and rural areas with poor sanitation. Adults with lower socioeconomic level have higher immunogenicity and more asymptomatic HAV infection, and vice versa (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) .\u003c/p\u003e \u003cp\u003eThe Reoviridae family of viruses, which includes rotaviruses, is divided into seven groups (A-G). In underdeveloped nations in Africa, Asia, and Latin America, it is estimated that there are 744\u0026nbsp;million to 1\u0026nbsp;billion cases of diarrhea and 2.4\u0026nbsp;million to 3.3\u0026nbsp;million fatalities among children under the age of five per year. This equates to 6,600 to 9,000 deaths every day. The most common cause of severe gastroenteritis in children under five years of age in developing and industrialized and less developed countries are rotaviruses (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHAV and Rotavirus vaccinations are now accessible. There are presently two approved oral rotavirus vaccinations on the market (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e): RotaTeq\u0026reg; from Merck (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) and Rotarix\u0026reg; from GlaxoSmithKline (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). In contrast, there are three approved HAV vaccines, including the inactivated combination vaccination Twinrix and the single-antigen vaccines Havrix and Vaqta (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). The safety and effectiveness of all three vaccinations, which are created from inactivated HAV, are equivalent. The use of these vaccinations is presently authorized in the US. Although vaccinations against these viruses have been produced, not all people, especially in low-income countries, have access to them (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). This emphasizes how urgently more work has to be done to guarantee that vaccinations are available and inexpensive for all populations, regardless of their financial situation (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) .\u003c/p\u003e \u003cp\u003eThe VP1, VP2, VP3, and VP4 capsid proteins are all present in 60 copies in the capsid of the hepatitis A virus (HAV) (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). The interaction between the exterior surface of the constructed capsid and a receptor on the surface of the host cell is necessary for the virus to enter the cell. The capsid surface also interacts with the host's antibodies, which may be able to neutralize the virus and stop infection. 42 antigenic areas of the HAV polyprotein were discovered using peptide mapping in earlier investigations (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Numerous investigations have demonstrated that VP1 stimulates the development of antibodies that are neutralizing (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). As a result, it is thought that the VP1 protein may be a candidate for a recombinant vaccination (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Rotavirus, on the other hand, has a segmented genome that codes for six structural and six nonstructural proteins (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). The outer surfaces of the virions include the two key structural proteins VP4 and VP7 (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). By way of proteolytic cleavage, VP4 is split into two subunits, VP5 and VP8 (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). It is thought that VP8* plays a key role in viral attachment to host cells (\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe study of peptide-based vaccinations has grown in popularity. Long peptides with immunodominant epitopes may be employed as vaccines if they can stimulate both humoral and cellular immunity against a variety of serological types (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). The terms \"multivalent\" and \"multivalent vaccine\" are frequently used imprecisely to refer to two distinct vaccine types (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e): one that may provide protection against numerous illnesses with a single vaccine and one that can provide protection against multiple strains of a single pathogen (\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Because they can protect against several illnesses with fewer injections, lower the cost of healthcare and patient care, and streamline vaccination programs while preserving the effectiveness and safety of single-component vaccines, efficient multivalent vaccines are highly desired (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). It is vitally necessary to develop a multivalent peptide-based vaccination against HAV and rotavirus, especially in low-income nations where the illness burden is high and access to clean water and healthcare is constrained (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eBioinformatics tools of multi-domain analysis, essential estimation in fusion protein production to elucidate immunologically conserved residues, lead to the emergence of new disciplines in the field of immunoinformatics-based multi-epitope vaccine design and construction (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e), such as epitope prediction, efficacy analysis, safety, it provides the effects of toxicity without the need for the growth of pathogenic agents and thus accelerates the vaccine development process (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe goal of this work is to create a new, recombinant VP8*-rotavirus\u0026thinsp;+\u0026thinsp;AAY\u0026thinsp;+\u0026thinsp;HAV-VP1 fusion protein utilizing a flexible linker with a proteasome-cleavable site. This protein combines VP4 (VP8*) with the immunodominant portions of VP1. This strategy is to develop a bivalent vaccination candidate that may concurrently protect against rotavirus and the hepatitis A virus.\u003c/p\u003e \u003cp\u003eSuccess of such a vaccine would depend to a large extent on the antigenic peptide to be used in antibody production. The non-glycosylated protein VP4 on the surface capsid of the virus is important in Rota viral immunogenicity and the major antigenic site(s) responsible for neutralization of the virus via VP4 is in the VP8* subunit of VP4. It is necessary that the peptide should be very specific and a peptide sequence which would stimulate both the T and B immunogenic cells would provide maximum protection against the virus. Advanced computational techniques and existing databases of sequences of the VP4 protein of rotavirus help in identification of such specific sequences. Using an Insilco approach, we have identified a highly conserved VP8* subunit of the VP4 surface protein of rotavirus which shows both T and B cell processivity and is also non-allergenic. This sub-unit could be used in \u003cem\u003ein vivo\u003c/em\u003e models for induction of antibodies(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) G1P[8] rotavirus strain As the dominant strain responsible for the spread of rotavirus infection in Iran and other parts of the world, we consider it in this study.\u003c/p\u003e"},{"header":"MATERIAL AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Amino Acid Sequence Retrieval\u003c/h2\u003e \u003cp\u003eThe VP1-HAV (NP_740552.1), VP8* rotavirus G1P[8] (NCBI accession number:ALU63988.1), CAC14074.3 (IIIA), AAU87586.1 (IIA), BAF37541.1 (IIIB), AAK44219.2 (IIB), and AF314208.1 (IB) sequences were obtained in FASTA format from GenBank of the National Centre for Biotechnology Information (NCBI)(\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Determination of Conserved Regions\u003c/h2\u003e \u003cp\u003eThe obtained sequences were aligned using MEGA6.0 ClustalW and the multiple sequence alignment (MSA) program to determine the degree of conservation. Using the Bio edit tool, MSA was visualized (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Prediction of T-cell Epitopes in BALB/c and Human\u003c/h2\u003e \u003cp\u003eWe used a combined peptide library to evaluate and evaluate matrices (Comblib Sidney2008) and submitted the acquired sequences to the IEDB's MHCI- and MHCII-binding prediction tool (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://tools.iedb.org/mhc/n\u003c/span\u003e\u003cspan address=\"http://tools.iedb.org/mhc/n\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) using a variety of techniques, including artificial neural networks (ANN), stabilized matrix methods (SMM), and SMM. Additionally incorporated were Rank PEP server and MHC-NP net CTLpan1.1 server. Results from all employed procedures all came within a similar range.\u003c/p\u003e \u003cp\u003eT-cell epitope lengths were set at 9 mers for MHC class I and 15 mers for MHC class II for BALB/c and human, respectively. The MHC class I alleles for BALB/c were H2-Dd, H2-Kd, and H2-Ld, whereas the MHC class II alleles were H2-IAd and H2-IEd. Based on the diversity of antigens and the level of identification by the variable HLA molecules in a population, as well as the most prevalent HLA in the Persian population based on the available report, HLA-A*01, 02, 03, 11, 24, 26, 32, HLA-B*35, 51, 50, 27, 57, and HLA-DRB1*15, 11, 13, 03, 04, 07 were selected for MHC class I and MHC class II, respectively.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Predictions of Antigenicity, Immunogenicity, Population Coverage, and Epitope Conservancy\u003c/h2\u003e \u003cp\u003eThe antigenicity scores of discovered epitopes were assessed using the online VaxiJen v2.0 antigen prediction programme (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e), which enables the arrangement of antigens according to the physicochemical properties of the protein without the need for sequence alignment. Antigenic scores greater than 0.5 4 were used to define such epitopes. Through the IEDB tool in the Iranian population (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://tools.iedb.org/population/\u003c/span\u003e\u003cspan address=\"http://tools.iedb.org/population/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e), the predicted peptides interacting with MHC I and II molecules in the considered area were investigated (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2\u0026ndash;5. Toxicity and Allergenicity Analyses\u003c/h2\u003e \u003cp\u003eWe evaluated the toxicity of the selected model using ToxinPred (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e). This tool may be used to check all physicochemical properties to confirm that epitopes are safe for the host. The allergenicity was examined using AllerTOP v.2.0 (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2\u0026ndash;6. Prediction of linear and Conformational B-cell Epitopes\u003c/h2\u003e \u003cp\u003eThe BepiPred (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e) linear epitope prediction service from the Immune Epitope Database was used to forecast linear B cell epitopes with a threshold of 0.35 and lengths ranging from 6 to higher residues. The approaches for identifying various physicochemical characteristics of amino acids, such as antigenicity, surface accessibility, flexibility, hydrophilicity, and beta-turns, were also evaluated using the tools of the Immune Epitope Database (IEDB) Analysis Resource (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://tools.iedb.org/bcell\u003c/span\u003e\u003cspan address=\"http://tools.iedb.org/bcell\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) platform. The protein sequence scanning window was extended in all approaches to 389 residues. With a minimum score of 0.50, we utilized the IEDB online programme ElliPro to predict discontinuous B-cell epitopes. This technique predicts epitopes by taking into account both structure- and sequence-based information.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.7. Primary and secondary Structure Assessment\u003c/h2\u003e \u003cp\u003eThe physicochemical characteristics of the fragments, including their weight, aliphatic index, Grand average of hydropathicity (GRAVY), theoretical pI, and atomic composition, were examined using Expasy's ProtParam service. The self-optimized prediction method with alignment (SOPMA) and Jpred tools were used to assess the secondary structure of the proteins' a-helix, b sheets, and random coils (\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e2.8. Homology Modeling and Validation\u003c/h2\u003e \u003cp\u003eThe Threading ASSEmbly Refinement (I-TASSER) online server programmes were developed by Zhang Y. (2008). Protein 3D Structure Prediction I-Tasser Server. IntFOLD Integrated Protein Structure and Function Prediction Server (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e), which provides 3D models as well as a confidence score (C-Score) and a model quality score, was used in the analysis of the 3D models (BMC Bioinformatics). Then, an analysis of the three DFIRE2 indicators\u0026mdash;energy profile, C-score, and stereochemical qualities\u0026mdash;was conducted (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e). Utilizing the GalaxyRefine server (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://galaxy.seoklab.org/\u003c/span\u003e\u003cspan address=\"http://galaxy.seoklab.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e), the projected vaccine build model will be improved and refined(\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e). The ProSA-web server was used to evaluate the three-dimensional model (\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e) (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://prosa.services.came.sbg.ac.at/prosa.php\u003c/span\u003e\u003cspan address=\"https://prosa.services.came.sbg.ac.at/prosa.php\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). Additionally, the Ramachandran graph of the three-dimensional structure was created using the MolProbity service (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://molprobity.biochem.duke.edu/\u003c/span\u003e\u003cspan address=\"http://molprobity.biochem.duke.edu/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) (\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e2.9. Molecular Docking Analysis\u003c/h2\u003e \u003cp\u003eTo activate innate immune cells in antiviral responses, Toll-like receptors (TLRs) are used as integral membrane proteins on innate immune effector cells. TLR3 and TLR4 can recognize structural glycoproteins and specific forms of viral nucleic acids and nonstructural proteins, leading to the release of inflammatory cytokines, and are important in recognizing viral genetic material in end lysosomal compartments to initiate antiviral responses (\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e). To understand the interaction between their structure and TLRs, we obtained the crystal structures of TLR3 and TLR4 from the Protein Data Bank using PDB IDs 3FXI and 1Z1W. Subsequently, we used the ClusPro 2.0 server, which is based on the PIPER Fast Fourier Transform (FFT) correlation method, to bind TLR3 and TLR4 to vaccine protein as ligands for binary interaction. The docking process obtained 30 models through three sequential steps: rigid-body docking, cluster-preserving structures, and refinement using CHARMM minimization. The best cluster was selected based on the lowest score. Finally, PyMOL was used to visualize binding structures and evaluate interactions between TLRs and vaccines (\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThe Iranian population\u0026apos;s highly preserved VP8*-rotavirus\u0026thinsp;+\u0026thinsp;AAY\u0026thinsp;+\u0026thinsp;HAV-VP1 fusion protein areas were chosen. The variable sections were removed in order to produce the most appropriate shortened version of HAV, and as a result, amino acids 99 to 259 in the VP1 alignment comprised the most conserved amino acids throughout the clades. Additionally, the viral VP8* amino acids 68 to 277 were used. This study led to the selection of VP8*-rotavirus\u0026thinsp;+\u0026thinsp;AAY\u0026thinsp;+\u0026thinsp;HAV-VP1 fusion protein for further evaluation.\u003c/p\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n \u003ch2\u003e3.1. MHC Class I and II Binding Prediction in BALB/c and Human\u003c/h2\u003e\n \u003cp\u003eTo design a more efficient and high-throughput vaccination model, we looked at the 9 m coverage of T-cell epitopes in BALB/c. (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). According to the IEDB recommendations, the MHC-NP, net CTLpan1.1, RANKPEP, and netMHCpan3.0 servers were utilized to anticipate the potential epitopes. T-cell epitopes were evaluated using a variety of methods to improve prediction precision. High affinity peptides with the antigenic characteristic (percentile rank 1) are indicated as a result of the findings in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. Accordingly, of the 42 MHC class I epitopes in our construct, 29 were found to be antigenic in BALB/c, and for MHCII, 6 epitopes were predicted (percentile rank 1), of which WTAVVAIEPHVNPVD, IHSEFYIIPRSQESK, and TAVVAIEPHVNPVDR were antigenic epitopes.\u003c/p\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"564\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAllele\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePeptide\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eStart\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEnd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePercentile rank\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAntigenicity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Ld\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003eLPSTLRWFF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e252\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e260\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Dd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRGPLDLTII\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e267\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e275\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.20\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Kd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNYNHSDEYL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e364\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e372\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.47\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Kd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEYLSFSCYL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e370\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e378\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.53\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Dd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHGLPSTLRW\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e258\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.42\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Dd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003eFTPPNDYWI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Dd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eISITIHSEF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e129\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e137\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.26\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Ld\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003ePPHGLPSTL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e248\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e256\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Ld\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGPLDLTIII\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e268\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e276\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.54\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Dd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRNDSNKWKF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.04\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Kd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003eRWFFNLFQL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e257\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e265\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Kd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003eKYGGRVWTF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Ld\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNPVDRQYTI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.93\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Ld\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eISITIHSEF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e129\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e137\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.26\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Dd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003eSTSNPPHGL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e244\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e252\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Dd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003eTPPNDYWIL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Dd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSNKWKFLEM\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.67\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Ld\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003eTPPNDYWIL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Dd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eKEYTFPITL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e234\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e242\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.29\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Dd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSTLRWFFNL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e254\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e262\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.71\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Dd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTSDTRLVGI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.78\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Dd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNSNNKEYTF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e230\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e238\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.97\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Dd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRTGNIQIRL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e323\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e331\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.84\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Ld\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMAWFTPVGL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e285\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e293\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.31\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Ld\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eKEYTFPITL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e234\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e242\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.29\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Kd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003eSYLYAVSGA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e335\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e343\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Kd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003eKFGNSIVKM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e208\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e216\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Kd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003eKEYTFPITL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e234\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e242\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.23\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Dd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIIVSKTSLW\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e186\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e194\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.52\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Dd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVGLAVDTPW\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e291\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e299\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.53\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Dd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003eYNRDIIIRF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e199\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e207\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Kd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIRLPWYSYL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e329\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e337\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.71\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Kd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTFGLVSIQI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e354\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e362\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.09\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Dd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLSIDYKTAL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e306\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e314\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.47\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Dd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eKTALGAVRF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e311\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e319\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.89\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Kd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eWFTPVGLAV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e287\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e295\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.40\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Dd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSSTANLNNI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e121\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e129\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.68\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Dd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003eRTLTSDTRL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Kd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIRFKFGNSI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e205\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e213\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.14\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Kd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eYRGPLDLTI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e266\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e274\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Ld\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003eLPWYSYLYA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e331\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e339\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.957446808510639%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eH-2-Kd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRFKFGNSIV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e206\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e214\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.425531914893616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.46\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e*Antigenicity scores \u0026ge; 0.4 are shown in bold\u003c/p\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e\u003cem\u003e\u0026nbsp;In silico\u003c/em\u003eanalysis of predicted BALB/c MHC class \u0026Iota;.\u003cdiv align=\"char\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"687\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eAllele\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003ePeptide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003eStart\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003eEnd\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003ePercentile rank\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eToxicity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003eAntigenicity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eAllergenicity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*02:06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eAIEPHVNPV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e1.0847\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*02:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*01:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eANYNHSDEY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e363\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e371\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e0.5623\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*26:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*02:06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eAVVAIEPHV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e0.7941\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*02:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*26:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eDIIVSKTSL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e185\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e193\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e0.8737\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-B*35:03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-B*51:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eDSTFGLVSI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e352\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e360\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e1.9570\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*11:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eESALSIDYK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e303\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e311\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e1.8557\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*24:02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eEYLSFSCYL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e370\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e378\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e1.5388\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-B*51:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eGPLDLTIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e268\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e276\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e1.5477\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-B*35:03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-B*57:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHGLPSTLRW\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e258\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e0.4250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-B*50:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eIDYKTALGA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e308\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e316\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e1.3147\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*32:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e186\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e194\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e0.5202\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-B*57:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eIIVSKTSLW\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*26:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*24:02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-B*27:02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eIRFKFGNSI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e205\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e213\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e1.1449\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*32:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eKTALGAVRF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e311\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e319\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e0.8993\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-B*57:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*24:02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*01:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eKTDSTFGLV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e350\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e358\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e1.6797\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*02:06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-B*35:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eLGDKTDSTF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e347\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e355\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e1.3270\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*11:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eLSSRSIQYK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e170\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e1.1724\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*03:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*26:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e357\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e365\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-B*35:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;LVSIQIANY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e1.4207\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*01:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*02:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e133\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*32:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eNLNNISITI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e1.7404\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*02:06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-B*57:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e230\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e238\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e0.9777\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-B*35:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eNSNNKEYTF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*32:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*26:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eNSNTNGVVY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e0.3576\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-B*51:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003ePPIQNTRNV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e157\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e165\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e1.5373\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*32:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eRDIIIRFKF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e201\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e209\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e1.5910\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*32:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eRTGNIQIRL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e323\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e331\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e1.8437\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-B*57:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*11:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eSSRSIQYKR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e171\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e179\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e0.8972\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-B*51:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eTANLNNISI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e123\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e131\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e1.2061\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-B*35:03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-B*50:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eTEQSEFYFP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e381\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e389\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e0.6569\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*24:02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eTFGLVSIQI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e354\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e362\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e2.0992\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-B*35:03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eTPWVEKESA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e297\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e305\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e0.4216\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-B*35:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-B*50:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eVEKESALSI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e308\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e1.0647\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*02:06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eYINNGLPPI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e151\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e159\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e0.9097\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003eNon-Allergen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003eHLA-A*02:01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.429403202328967%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.315866084425036%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644832605531295%\" valign=\"top\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.372634643377001%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.809315866084425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.701601164483261%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e*Antigenicity scores \u0026ge; 0.4 are shown in bold.\u003c/p\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003ePredicted MHC class \u0026Iota; epitopes in human.\u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003eUsing the IEDB MHC prediction tool, the truncated VP8-VP1 protein sequence was compared to human MHC class I and II with well-known HLAs in the Persian population. Tables \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e illustrate, respectively, the binding peptides for MHC class I (29 epitopes) and II (29 epitopes), some of which interact with several HLAs. Finally, neither the class I nor the class II HLA binders were poisonous nor allergenic.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"center\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"119%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAllele\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePeptide\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eStart\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEnd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"top\"\u003e\n \u003cp\u003ePercentile rank\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eToxicity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAllergenicity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAntigenicity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*11:53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eAYTFNSNNKEYTFPI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e226\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e240\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*03:27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eCNEYINNGLPPIQNT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e148\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e162\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*13:62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eDTRLVGILKYGGRVW\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*03:40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eEKESALSIDYKTALG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e301\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e315\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e1.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*03:05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eEMQYNRDIIIRFKFG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e196\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e210\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*11:17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eEPHVNPVDRQYTIFG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e1.25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*03:19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eFYNRRTLTSDTRLVG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*04:66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eHSEFYIIPRSQESKC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e134\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e148\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*04:89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eIQYKRAQVNEDIIVS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e175\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e189\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*03:27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eKCNEYINNGLPPIQN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e147\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e161\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*03:38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eKESALSIDYKTALGA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e302\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e316\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e1.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*07:06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eLDLTIIITGATDVDG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e270\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e284\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*03:27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eNEYINNGLPPIQNTR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e149\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e163\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*04:51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eNGVVYESTNNSDFWT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e-0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*04:09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eNTNGVVYESTNNSDF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*07:11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003ePLDLTIIITGATDVD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e269\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e283\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*04:27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eRSIQYKRAQVNEDII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e173\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e187\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*11:27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eSDTRLVGILKYGGRV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e106\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*11:81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eSEFYIIPRSQESKCN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e135\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e149\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*13:10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eSIQYKRAQVNEDIIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e174\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e188\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*04:82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eSRSIQYKRAQVNEDI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e172\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e186\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*04:14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eSSQNEFYNRRTLTSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*04:87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eSSRSIQYKRAQVNED\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e171\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e185\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*04:07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eTNGVVYESTNNSDFW\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*11:54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eTSDTRLVGILKYGGR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*13:32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eVVAIEPHVNPVDRQY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e1.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003eHLA-DRB1*04:07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003eWSAAYTFNSNNKEYT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e223\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\" valign=\"bottom\"\u003e\n \u003cp\u003e237\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003eNon-Toxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003eNON ALEERHEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e*Antigenicity scores \u0026ge; 0.4 are shown in bold.\u003c/p\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e:\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ePredicted MHC class I\u0026Iota; binders in human\u0026nbsp;\u003cdiv align=\"char\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"char\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cimg src=\"https://myfiles.space/user_files/122228_c8a1650c59388082/122228_custom_files/img1709121528.png\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003eB cells produce antibodies as part of humoral immunity. Long-lasting immunity is provided through B-cell receptors\u0026apos; recognition of B-cell epitopes. The ABCpred server discovered 26 epitopes with a score of 0.5 or higher and a length of 16 mer, which the BepiPred tool then verified. Their hydrophilicity, surface accessibility, antigenicity, flexibility, and beta-turn were used to describe them. The mean scores for Emini surface accessibility, Karplus and Schulz flexibility, Parker hydrophilicity, and Kolaskr and tongaonkar antigenicity were determined to be 1.000 (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ea), 1.000 (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eb), 1.296 (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ec), and 1.016 (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ee), respectively. At the same time, Chou and Fasman\u0026apos;s method was utilized to forecast beta-becomes since beta turns hydrophilic and aids in triggering the immunological response (Rose et al., 1985). The mean, lowest, and highest beta-turn scores were 1.020, 0.641, and 1.407, respectively (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ed). The Ellipro server produced six conformational and thirteen linear B-cell epitopes (Tables \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e and 5). PyMOL examined the mapped epitopes.\u003c/div\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n \u003ch2\u003e3.2. Antigenicity, Immunogenicity, Population Coverage, and Epitope Conservancy Analysis\u003c/h2\u003e\n \u003cp\u003eAn immune-prophylactic vaccine must meet the key requirement of antigenicity. The antigenicity of the suggested vaccine construct was assessed using VaxiJen 2.0 servers to make sure that it would engage with the B and T cell receptors to trigger a sustained immune response. Due to the findings in Tables \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, and \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, high-affinity peptides with the antigenic characteristic (percentile rank 1) are included. Table\u0026nbsp;5 contains the findings of the overall population coverage in the Persian population.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\n \u003ch2\u003e3.3. Primary and Secondary Structure Analysis\u003c/h2\u003e\n \u003cp\u003eThe fusion protein with molecular weight and specific model, which is the theoretical isoelectric point, and the hydropathic average - indicating the solubility and hydrophobicity of the desired protein - were calculated using the ProtParam Expasy service. The fusion model has 35 positively charged (Arg\u0026thinsp;+\u0026thinsp;Lys) and 34 negatively charged (Asp\u0026thinsp;+\u0026thinsp;Glu) residues in a polypeptide with a molecular weight of 44.42 kDa and 389 amino acids. This model is also projected to be hydrophilic and dissolvable (GRAVY Great Normal of Hydropathy: -0.397). Using secondary structure analysis and disulfide connections, the SOPMA programme was utilized to predict the secondary structure of Model characteristics such as beta turns, helices, random coil contribution, and C-score. A larger ratio of random coils to extended strands is associated with an increase in the production of protein antigenic epitopes. As a result, 15.17 percent of it is a helix, and 35.48 percent of it is a sheet, which, along with the largest percentage of random coils (42.16) can produce greater antigenic epitopes. Fusion Protein Model predicts the presence of a single disulfide bridge between and that offers stability external to the cell.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\n \u003ch2\u003e3.4. Tertiary Structure Prediction and Validation\u003c/h2\u003e\n \u003cp\u003eModel\u0026apos;s three-dimensional structure was predicted using the online I-TASSER service, which provides five top models with C-scores ranging from \u0026minus;\u0026thinsp;5 to 2. The model with the greatest C-score is the most effective one. This value\u0026apos;s confidence level was adequate (-1.06) for the model that was chosen. Using PyMOL, the protein picture was produced. Additionally, the Ramachandran plot demonstrated that 271/387, or 70.0%, of all residues, were in favored areas. A total of 338/387 residues, or 87.3%, were in permitted locations (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). The model\u0026apos;s 3D structure had a Z-score of 6.04 (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\n \u003ch2\u003e3.9. Molecular Docking\u003c/h2\u003e\n \u003cp\u003eToll-like receptors (TLRs) are very important for recognizing pathogen-related molecular patterns and regulating the induction of immune responses in viral infections, especially hepatitis A and rotavirus. In this study, out of two Toll-like receptors (TLRs) (4 TLR3,) that TLR3 recognizes viral glycoproteins and lipoproteins and activates immune cells. Activation of TLR4 leads to inflammation and secretion of inflammatory cytokines such as interleukin-6 and 5 through a MyD88-related pathway and also promotes gamma interferon secretion through a MyD88-independent pathway. On the other hand, activation of TLRs-related immune pathways could be therapeutic for hepatitis A rotavirus infections. To evaluate the candidate vaccine binding affinity with TLRs, we used the ClusPro v2.0 binding tool, which is very helpful for evaluating the induction and immune responses. For each TLR binding vaccine design, thirty anchor complexes were generated and the corresponding centers and their lowest energy score was determined. Vaccine/TLR3 and vaccine/TLR4 complexes showed the center score and the lowest energy. The final output with the lowest global energy (-1089) for the vaccine/TLR3 construct and (-1006.8) for our vaccine/TLR4 construct was considered the most favorable interaction. Interactions between vaccine candidates and TLRs were visualized using PyMOL (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eHighly infectious viruses like rotavirus and hepatitis A can generate seasonal epidemics and pose a serious risk to the public's health. These viruses are able to easily cross boundaries and infect a variety of organisms. As a result, it is crucial to put in place efficient preventative measures, such vaccinations. Unfortunately, the lack of a bivalent vaccination highlights the necessity for a vaccine or pharmacological intervention to manage these epidemics notwithstanding the high fatality rates and astronomical medical costs associated with these infections (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). In contrast to traditional vaccination procedures that depend on attenuated or inactivated viral strains, bioinformatics analysis offers a speedier and less complex process for creating recombinant vaccines. The bioinformatics method offers a quicker and more effective technique to find possible vaccine epitopes (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn this study, we identified functional epitopes of a fusion protein of rotavirus and hepatitis A viruses (VP8*-rotavirus\u0026thinsp;+\u0026thinsp;AAY\u0026thinsp;+\u0026thinsp;HAV-VP1 fusion protein), including 389 amino acids with high immunogenicity to stimulate T cells and B cells, using advances in bioinformatics tools, the availability of viral genome databases, and previous studies.\u003c/p\u003e \u003cp\u003eFor rotavirus and hepatitis A, many vaccinations have been investigated. While full-length or truncated VP8* proteins and clinical studies with the p2*- VP8 (two fused VP8* copies) subunit vaccine have also showed promising outcomes, recombinant VP6 proteins have been studied as vaccine candidates for rotavirus. Previous research has examined the effectiveness of Vi-VP8 (comprising many rotavirus groups) combinations in boosting the immune response with a focus on various rotavirus species. According to Mickley \u003cem\u003eet al\u003c/em\u003e., the Vi-VP8 conjugation could induce persistent immunity and had a molecular weight of 49.50 kDa. However, Dormitzer \u003cem\u003eet al\u003c/em\u003e. (2002) noted that this strategy may not be successful due to the notable discrepancies between the antigenic epitopes of the VP8* region of rotavirus A strains circulating in different regions of the world. Because the VP8* fragment has more genetic diversity, is more effective against a variety of rotavirus A strains, offers long-term protection from the virus, and also triggers a potent and specific immune response against rotavirus A, we chose to concentrate on it rather than the VP4 fragment. (2012) Zeller et al.(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). According to earlier research and immunogenicity analyses, long-term booster doses of live, attenuated/inactivated hepatitis A vaccinations resulted in considerable seroconversion and protective protection. However, the sluggish rate of HAV proliferation in cell culture results in low yield, making the manufacture of inactivated vaccines challenging and expensive. In terms of safety, high purity, and well defined structures, recombinant subunit vaccines, which have the capacity to elicit an effective immune response, seem more sensible (\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRecombinant proteins can be used to identify particular epitopes, minimize the risk of adverse responses, and examine prospective epitopes in proteins, which provides the possibility of producing vaccines with high ability to fight effectively against diseases caused by viral agents(\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e) The discovered epitopes in this work have the capacity to trigger humoral immune reactions from memory B cells and to trigger particular immunological reactions against rotavirus and hepatitis A. They can also boost CTL and Th cell activity and produce CTL-mediated responses, which are crucial for controlling viral infection. The promotion of effective CD8\u0026thinsp;+\u0026thinsp;CTL responses and durable antibody immunological responses through the induction of T-cell-mediated immunity lowers the incidence of illness. Because these epitopes may elicit a potent and focused immune response against rotavirus and hepatitis A, their application in the creation of vaccines holds promise for stopping the spread of these viral diseases (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Analysis of the intended structure in revealed the expected epitopes' affinity for mouse MHC-I and II molecules. It was discovered that we have a large number of epitopes with the strongest affinity for binding to mouse MHC-I alleles, and molecular binding study revealed the Mouse alleles with the highest mutual similarity score were H-2-Ld, H-2-Dd, and H-Dd2. The antigenicity of the VP8* region's antigenic epitopes may be impacted by various amino acid variations in their exposed areas. The degree of T cell immunogenicity is significantly influenced by the T cell epitopes' ability to bind to the MHC. Since epitope binding to MHC molecules is necessary for antigen presentation to T cells, it is crucial to find epitopes that interact with MHC I and MHC II polymorphic alleles that have high population coverage scores.\u003c/p\u003e \u003cp\u003eSimilar research was done on rotavirus from vp7 and vp8, however only three CTL epitopes and four HTL epitopes were found in B cells. This emphasizes the significance of utilizing bioinformatics methods to locate possible vaccine epitopes since they can assist locate certain epitopes that might trigger robust and focused immune responses against viral infections. It is crucial to identify strong epitopes for the rotavirus and hepatitis A viruses in order to create vaccinations that are effective against these viral illnesses. Muhammad Osman as well as others. The strongest epitopes in this investigation were determined to be 9 CTL and HTL epitopes from 389 amino acids with the greatest binding affinities for various MHC molecules and high immunity and protection ratings. For instance, the Pol (215\u0026ndash;258) epitope has the maximum binding affinity for five HLA supertypes and 16 common HLA-I alleles. For a number of HLA-B and HLA-A alleles, the epitope also demonstrated strong binding affinity. The secondary and tertiary structures of the vaccine need epitopes connected to the TCR/BCR by the linker sequences AAY and EAAAK. It was discovered that the vaccine's structure comprises of 40% coiled-coil, 42% beta sheets, and 16% alpha helix (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe study looked at the physical and chemical characteristics of the vaccine structure, and it was discovered that it had an aliphatic index, a possible hydrophobicity, and a molecular weight of 44.42 kDa. The peptide's total hydropathic average (GRAVY) was 0.381, which designates it as hydrophilic. These traits show that the vaccine protein is thermally stable and appropriate for the rotavirus and hepatitis A vaccines. Alpha helices, extended strands, beta twists, and random helical structures were discovered in the vaccine's secondary and tertiary structures, which were also examined. The Ramachandran diagram's predictions indicated that the three-dimensional structure would have advantageous properties. The vaccine's structural flaws and potential modelling issues were corrected using the ProSA programme, which was also used to determine the structure's overall quality score.\u003c/p\u003e \u003cp\u003eThe linear epitope prediction was assessed by the amino surface accessibility, Kulascar and Tongaonkar antigenicity test, and Parker hydrophilicity test in order to establish that the vaccine binds to B cells. Epitopes over the threshold were anticipated, and it was discovered that the B cell's surface and epitopes were \"hydrophilic\". IEDB techniques were used to analyze the target sequence's expected MHC I and II binding to T cells, and it was discovered that T cells are projected to interact with MHC I alleles with an IC\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;100.However, the study also discovered that certain amino acid variations occur in the exposed areas of the VP8* region's antigenic epitopes, and these variations may have an impact on antigenicity. Therefore, more research and optimization may be needed to guarantee the vaccine's effectiveness. Assessment, which indicates that this model. The structural analysis of this model revealed that the model that received the highest score (0.994) contained a protein with 389 amino acids and 42.16% random coils. Additionally, the Ramachandran diagram revealed that there were 91.7% non-toxic amino acids in the protein, with a high population coverage, particularly in Iran and Europe. Performance evaluation of protein-protein binding affinity, protein fusion candidate vaccine with mediators of innate immune stimulation actually interacts with rotavirus VP1-HAV (\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e)and rotavirus, VP8(\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e) genes with Toll-like receptors (TLRs) for pathogen recognition (eg, TLR3, TLR4) showed that the interaction between the fusion protein can lead to the induction of the release of inflammatory cytokines such as interleukin 6 and 5, as well as promoting the release of gamma interferon and creating an effective innate immune response, which indicates the good performance of the fusion protein as a vaccine candidate against the spread of hepatitis A virus (\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e). that the accuracy of the desired study requires experimental and clinical validation. Immunity against diseases is developed by vaccination, which also provides antigenic agents to activate the immune system. On the other hand, immunoinformatic approaches are a very effective tool for designing and studying algorithms to reduce time and cost, as well as the trend of increasing the propagation chain of rotavirus infection and the prevalence of hepatitis A in children. At the moment, there is no effective drug and the time-consuming process of treatment and drug. And the only way to regulate the poor economic conditions in emerging and third-world nations is by offering a possible vaccination. We created a protein fusion as a possible dual vaccination candidate using bioinformatics tools and methodologies (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). The chosen recombinant protein is next tested \u003cem\u003ein vitro\u003c/em\u003e and \u003cem\u003ein vivo\u003c/em\u003e to see how strongly it can elicit immunological responses. It may be utilized efficiently to create vaccines quickly and affordably. Although the Insilco results show that the vaccination is efficacious, laboratory testing and animal model studies need be done to evaluate the vaccine's therapeutic efficacy. Additionally, the use of anticipated peptides may result in the creation of native variant DNA vaccines. For \u003cem\u003ein vitro\u003c/em\u003e and \u003cem\u003ein vivo\u003c/em\u003e investigations, particular attention should be paid to residues that exhibit minimal variability, stimulate B-cell immunity, and have a high affinity to alleles. Additionally, the variety of projected epitopes will rise as a result of the research of molecular epidemiology in many worlds logical systems. As a result, we advise conducting further fieldwork, particularly in nations where there is little knowledge about the rotavirus and hepatitis A strains that are in circulation. It will then be put to use in research.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eWe designed a fusion protein using bioinformatics tools and methods as a viable recombinant vaccination candidate. Hepatitis A virus VP1 and rotavirus VP8 protein epitopes are present in this vaccination. The chosen recombinant protein can substantially elicit immunological responses and may help in the development of an efficient vaccine to decrease the prevalence of rotavirus and hepatitis A in various populations.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData Availability declaration:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data supporting the findings of this study are available within the paper and its Supplementary Information.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eACKNOWLEDGEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank all of the staffs at Hepatitis and AIDS Dept. of Pasteur Institute of Iran who participated in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONFLICT OF INTERESTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interests.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eOrganization WH. WHO immunological basis for immunization series: module 18: hepatitis A. 2019.\u003c/li\u003e\n\u003cli\u003eDamtie D, Melku M, Tessema B, Vlasova AN. Prevalence and genetic diversity of rotaviruses among under-five children in Ethiopia: A systematic review and meta-analysis. Viruses. 2020;12(1):62.\u003c/li\u003e\n\u003cli\u003eIzadi M, Esfahani AA, Hassannia H, Jafari NJ, Najarkolaei FR, Rezaee-Zavareh MS. Seroprevalence of hepatitis A virus among Iranian soldiers. Gastroenterology and hepatology from bed to bench. 2016;9(2):100.\u003c/li\u003e\n\u003cli\u003eJacobsen KH. Globalization and the changing epidemiology of hepatitis A virus. Cold Spring Harbor Perspectives in Medicine. 2018;8(10).\u003c/li\u003e\n\u003cli\u003eArıstegui J, Dal-Re R, Dıez-Delgado J, Mares J, Casanovas J, Garcıa-Corbeira P, et al. Comparison of the reactogenicity and immunogenicity of a combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polio (DTPa\u0026ndash;HBV\u0026ndash;IPV) vaccine, mixed with the Haemophilus influenzae type b (Hib) conjugate vaccine and administered as a single injection, with the DTPa\u0026ndash;IPV/Hib and hepatitis B vaccines administered in two simultaneous injections to infants at 2, 4 and 6 months of age. Vaccine. 2003;21(25-26):3593-600.\u003c/li\u003e\n\u003cli\u003ePlosker GL. Rotavirus Vaccine RIX4414 (Rotarix\u0026trade;) A Pharmacoeconomic Review of its Use in the Prevention of Rotavirus Gastroenteritis in Developing Countries. Pharmacoeconomics. 2011;29:989-1009.\u003c/li\u003e\n\u003cli\u003eAshur Y, Adler R, Rowe M, Shouval D. Comparison of immunogenicity of two hepatitis A vaccines\u0026mdash;VAQTA\u0026reg; and HAVRIX\u0026reg;\u0026mdash;in young adults. Vaccine. 1999;17(18):2290-6.\u003c/li\u003e\n\u003cli\u003eWang X, Xu W, Hu Y, Yao H, Xu L, Ma M, et al. Immunogenicity persistence of hepatitis A vaccines Healive\u0026reg; and Havrix\u0026reg; among children: 15 years follow-up and long-term prediction. Human Vaccines \u0026amp; Immunotherapeutics. 2023:2227549.\u003c/li\u003e\n\u003cli\u003eOtt J, Wiersma S. Single-dose administration of inactivated hepatitis A vaccination in the context of hepatitis A vaccine recommendations. International Journal of Infectious Diseases. 2013;17(11):e939-e44.\u003c/li\u003e\n\u003cli\u003eSagliocca L, Amoroso P, Stroffolini T, Adamo B, Tosti ME, Lettieri G, et al. Efficacy of hepatitis A vaccine in prevention of secondary hepatitis A infection: a randomised trial. The Lancet. 1999;353(9159):1136-9.\u003c/li\u003e\n\u003cli\u003eAmroabadi MA, Rahimi E, Shakerian A, Momtaz H. Incidence of hepatitis A and hepatitis E viruses and norovirus and rotavirus in fish and shrimp samples caught from the Persian Gulf. Arquivo Brasileiro de Medicina Veterin\u0026aacute;ria e Zootecnia. 2021;73:169-78.\u003c/li\u003e\n\u003cli\u003eNain A, Kumar M, Banerjee M. Oligomers of hepatitis A virus (HAV) capsid protein VP1 generated in a heterologous expression system. Microbial Cell Factories. 2022;21(1):1-12.\u003c/li\u003e\n\u003cli\u003ePeak CM, Stous SS, Healy JM, Hofmeister MG, Lin Y, Ramachandran S, et al. Homelessness and hepatitis A\u0026mdash;san diego county, 2016\u0026ndash;2018. Clinical infectious diseases. 2020;71(1):14-21.\u003c/li\u003e\n\u003cli\u003eSantos GMCd, Alves CR, Pinto MA, Amado Leon LA, Souza-Silva F. Detection of antibodies against hepatitis A virus (HAV) by a surface plasmon resonance (SPR) biosensor: a new diagnosis tool based on the major HAV capsid protein VP1 (SPR-HAVP1). Sensors. 2021;21(9):3167.\u003c/li\u003e\n\u003cli\u003eDOTZAUER R, VALLBRACHT A, KEIL GM. The proposed gene for VP1 of HAV encodes for a larger protein than that observed in HAV-infected cells and virions. Virology. 1995;213(2):671-5.\u003c/li\u003e\n\u003cli\u003eHu L, Crawford SE, Hyser JM, Estes MK, Prasad BV. Rotavirus non-structural proteins: structure and function. Current opinion in virology. 2012;2(4):380-8.\u003c/li\u003e\n\u003cli\u003eLi Y, Xue M, Yu L, Luo G, Yang H, Jia L, et al. Expression and characterization of a novel truncated rotavirus VP4 for the development of a recombinant rotavirus vaccine. Vaccine. 2018;36(16):2086-92.\u003c/li\u003e\n\u003cli\u003eHu L, Crawford SE, Czako R, Cortes-Penfield NW, Smith DF, Le Pendu J, et al. Cell attachment protein VP8* of a human rotavirus specifically interacts with A-type histo-blood group antigen. Nature. 2012;485(7397):256-9.\u003c/li\u003e\n\u003cli\u003eMohanty E, Dehury B, Satapathy AK, Dwibedi B. Design and testing of a highly conserved human rotavirus VP8* immunogenic peptide with potential for vaccine development. Journal of biotechnology. 2018;281:48-60.\u003c/li\u003e\n\u003cli\u003ePatton JT. Structure and function of the rotavirus RNA-binding proteins. Journal of General Virology. 1995;76(11):2633-44.\u003c/li\u003e\n\u003cli\u003eKabaabetswe L, Sebunya T, Matsheka M, Ndung\u0026apos;u T. Detection and molecular characterisation of group a rotavirus from children in northern Botswana. East African medical journal. 2005;82(4).\u003c/li\u003e\n\u003cli\u003eSkrobarczyk JW, Martin CL, Bhatia SS, Pillai SD, Berghman LR. Electron-beam inactivation of human rotavirus (HRV) for the production of neutralizing egg yolk antibodies. Frontiers in Immunology. 2022;13:840077.\u003c/li\u003e\n\u003cli\u003ePavitrakar DV, Atre NM, Tripathy AS, Shil P. Design of a multi-epitope peptide vaccine candidate against chandipura virus: An immuno-informatics study. Journal of Biomolecular Structure and Dynamics. 2022;40(2):648-59.\u003c/li\u003e\n\u003cli\u003eIsmail S, Ahmad S, Azam SS. Immunoinformatics characterization of SARS-CoV-2 spike glycoprotein for prioritization of epitope based multivalent peptide vaccine. Journal of Molecular Liquids. 2020;314:113612.\u003c/li\u003e\n\u003cli\u003eKuri PR, Goswami P. Current update on rotavirus in-silico multiepitope vaccine design. ACS omega. 2022;8(1):190-207.\u003c/li\u003e\n\u003cli\u003eUsman M, Ayub A, Habib S, Rana MS, Rehman Z, Zohaib A, et al. Vaccinomics Approach for Multi-Epitope Vaccine Design against Group A Rotavirus Using VP4 and VP7 Proteins. Vaccines. 2023;11(4):726.\u003c/li\u003e\n\u003cli\u003eMosa AI, Urbanowicz RA, AbouHaidar MG, Tavis JE, Ball JK, Feld JJ. A bivalent HCV peptide vaccine elicits pan-genotypic neutralizing antibodies in mice. Vaccine. 2020;38(44):6864-7.\u003c/li\u003e\n\u003cli\u003eLauer KB, Borrow R, Blanchard TJ. Multivalent and multipathogen viral vector vaccines. Clinical and Vaccine Immunology. 2017;24(1):e00298-16.\u003c/li\u003e\n\u003cli\u003eDutta K. Multi valent DNA vaccine against group A human rotavirus: an in-silico investigation. BioRxiv. 2020:2020.01. 13.903781.\u003c/li\u003e\n\u003cli\u003eHalsey NA. Safety of combination vaccines: perception versus reality. The Pediatric infectious disease journal. 2001;20(11):S40-S4.\u003c/li\u003e\n\u003cli\u003eSeo DJ, Lee MH, Son NR, Seo S, Lee KB, Wang X, Choi C. Seasonal and regional prevalence of norovirus, hepatitis A virus, hepatitis E virus, and rotavirus in shellfish harvested from South Korea. Food Control. 2014;41:178-84.\u003c/li\u003e\n\u003cli\u003eIkram A, Alzahrani B, Zaheer T, Sattar S, Rasheed S, Aurangzeb M, Ishaq Y. An in silico deep learning approach to multi-epitope vaccine design: a hepatitis E virus case study. Vaccines. 2023;11(3):710.\u003c/li\u003e\n\u003cli\u003eRodr\u0026iacute;guez M, Wood C, Sanchez-L\u0026oacute;pez R, Castro-Acosta RM, Ram\u0026iacute;rez OT, Palomares LA. Understanding internalization of rotavirus VP6 nanotubes by cells: towards a recombinant vaccine. Archives of virology. 2014;159:1005-15.\u003c/li\u003e\n\u003cli\u003eSayers EW, Cavanaugh M, Clark K, Pruitt KD, Schoch CL, Sherry ST, Karsch-Mizrachi I. GenBank. Nucleic acids research. 2021;49(D1):D92-D6.\u003c/li\u003e\n\u003cli\u003eTamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: molecular evolutionary genetics analysis version 6.0. Molecular biology and evolution. 2013;30(12):2725-9.\u003c/li\u003e\n\u003cli\u003eKundu S, Kumar V. Environmental DNA (eDNA) testing for detection of freshwater turtles in Temple pond. Herpetology Notes. 2018;11:369-71.\u003c/li\u003e\n\u003cli\u003eDoytchinova IA, Flower DR. Identifying candidate subunit vaccines using an alignment-independent method based on principal amino acid properties. Vaccine. 2007;25(5):856-66.\u003c/li\u003e\n\u003cli\u003eDoytchinova IA, Flower DR. VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC bioinformatics. 2007;8(1):1-7.\u003c/li\u003e\n\u003cli\u003eBui H-H, Sidney J, Dinh K, Southwood S, Newman MJ, Sette A. Predicting population coverage of T-cell epitope-based diagnostics and vaccines. BMC bioinformatics. 2006;7(1):1-5.\u003c/li\u003e\n\u003cli\u003eGupta S, Kapoor P, Chaudhary K, Gautam A, Kumar R, Consortium OSDD, Raghava GP. In silico approach for predicting toxicity of peptides and proteins. PloS one. 2013;8(9):e73957.\u003c/li\u003e\n\u003cli\u003eOluwaseun FA, Sibuyi NRS, Darius R. Immunoinformatics design of a novel epitope-based vaccine candidate against dengue virus. 2021.\u003c/li\u003e\n\u003cli\u003eJespersen MC, Peters B, Nielsen M, Marcatili P. BepiPred-2.0: improving sequence-based B-cell epitope prediction using conformational epitopes. Nucleic acids research. 2017;45(W1):W24-W9.\u003c/li\u003e\n\u003cli\u003eGeourjon C, Deleage G. SOPMA: significant improvements in protein secondary structure prediction by consensus prediction from multiple alignments. Bioinformatics. 1995;11(6):681-4.\u003c/li\u003e\n\u003cli\u003eYang Y, Zhou Y. Specific interactions for ab initio folding of protein terminal regions with secondary structures. Proteins: Structure, Function, and Bioinformatics. 2008;72(2):793-803.\u003c/li\u003e\n\u003cli\u003eHeo L, Park H, Seok C. GalaxyRefine: Protein structure refinement driven by side-chain repacking. Nucleic acids research. 2013;41(W1):W384-W8.\u003c/li\u003e\n\u003cli\u003eWiederstein M, Sippl MJ. ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic acids research. 2007;35(suppl_2):W407-W10.\u003c/li\u003e\n\u003cli\u003eChen VB, Arendall WB, Headd JJ, Keedy DA, Immormino RM, Kapral GJ, et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallographica Section D: Biological Crystallography. 2010;66(1):12-21.\u003c/li\u003e\n\u003cli\u003eLester SN, Li K. Toll-like receptors in antiviral innate immunity. Journal of molecular biology. 2014;426(6):1246-64.\u003c/li\u003e\n\u003cli\u003eRose PW, Beran B, Bi C, Bluhm WF, Dimitropoulos D, Goodsell DS, et al. The RCSB Protein Data Bank: redesigned web site and web services. Nucleic acids research. 2010;39(suppl_1):D392-D401.\u003c/li\u003e\n\u003cli\u003eKozakov D, Hall DR, Xia B, Porter KA, Padhorny D, Yueh C, et al. The ClusPro web server for protein\u0026ndash;protein docking. Nature protocols. 2017;12(2):255-78.\u003c/li\u003e\n\u003cli\u003ePollet J, Chen W-H, Strych U. Recombinant protein vaccines, a proven approach against coronavirus pandemics. Advanced drug delivery reviews. 2021;170:71-82.\u003c/li\u003e\n\u003cli\u003eKashyap P, Deka M, Medhi S, Dutta S, Kashyap K, Kumari N. Association of Toll-like receptor 4 with hepatitis A virus infection in Assam. Acta virologica. 2018;62(1):58-62.\u003c/li\u003e\n\u003cli\u003eFrias AH. Characterization of epithelial responses to rotavirus infection in the gut: Emory University; 2010.\u003c/li\u003e\n\u003cli\u003eNgoi SM. The opposing immunological effects of double-stranded RNA on cytotoxic CD8 T cell response: University of Connecticut; 2010.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table 4","content":"\u003cp\u003eTable 4 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Recombinant Vaccine, Immunoinformatic, Rotavirus, Hepatitis A Virus, Bivalent Vaccine","lastPublishedDoi":"10.21203/rs.3.rs-3952800/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3952800/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eHepatitis A virus (HAV) and rotavirus are mainly transmitted through fecal-oral and person-to-person contact, which cause severe gastrointestinal complications and liver diseases. This work used reverse vaccinology and immunoinformatic methods to create a novel bivalent vaccination against the rotavirus and HAV. The amino acid sequences of HAV-rotavirus proteins (VP1 and VP8*) were retrieved from GenBank. Multi-epitope DNA structures. Various computational approaches were employed to predict highly conserved regions and the most immunogenic B-cell and T-cell epitopes of VP8 and VP1 of rotavirus and HAV proteins in both humans and BALB/c. Moreover, the predicted fusion protein was analyzed regarding primary and secondary structures and homology validation. In this study, we used two highly conserved peptide sequences of VP8 and VP1 of rotavirus and HAV that induce T and B cell immunogenicity. According to T-cell epitope prediction, this area comprises 2713 antigenic peptides for HLA class II and 30 HLA class I antigenic peptides, both of which are virtually entirely conserved in the Iranian population. In this study, validation as well as analysis of the secondary and three-dimensional structure of the VP8*-rotavirus\u0026thinsp;+\u0026thinsp;AAY\u0026thinsp;+\u0026thinsp;HAV-VP1 fusion protein, with the aim of designing a multi-epitope vaccine with different receptors such as complications. TLR), 3,4 high immunogenic binding ability with immunological properties and interaction between multi-epitope target and TLR receptors were predicted, and it is expected that the target protein fusion has stable antigenic potency and compatible half-life. The above is suggested as universal vaccination programs.\u003c/p\u003e","manuscriptTitle":"Development of a Novel Bivalent Vaccine Candidate against Hepatitis A Virus and Rotavirus Using Reverse Vaccinology and Immunoinformatics","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-28 12:05:39","doi":"10.21203/rs.3.rs-3952800/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"
[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"47eb4efa-0fbd-425e-a375-52e4417039db","owner":[],"postedDate":"February 28th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-03-01T08:04:55+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-28 12:05:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3952800","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3952800","identity":"rs-3952800","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
Text is read by the "Ask this paper" AI Q&A widget below.
Extraction quality varies by source — PMC NXML preserves structure
cleanly, OA-HTML may include some navigation residue, and OA-PDF can
have broken hyphenation. The publisher copy
(via DOI)
is the canonical version.