Design of a Multi-Epitope Vaccine Against Chikungunya Virus: An InSilico Approach

Design of a Multi-Epitope Vaccine Against Chikungunya Virus: An InSilico Approach | 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 Design of a Multi-Epitope Vaccine Against Chikungunya Virus: An InSilico Approach ABHISHEK S R, Janani S P, Dr.Rama Chandra Prasad L.A This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7556626/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 The chikungunya virus (CHIKV) poses a re-emerging worldwide health risk marked by severe joint pain, with no specific antiviral therapies or widely available vaccines currently available. This requires the creation of new preventive strategies. Reverse vaccinology provides a robust and expedited method for the logical development of successful vaccine candidates. This research utilized an extensive computational framework to create a multi-epitope subunit vaccine. The target antigen chosen was the structural polyprotein of CHIKV (UniProt: Q8JUX5). Epitopes for B-cells, helper T-lymphocytes (HTL), and cytotoxic T-lymphocytes (CTL) were predicted and then refined according to elevated scores for antigenicity, immunogenicity, and the absence of allergenicity and toxicity. A concluding chimeric vaccine structure was created, featuring a beta-defensin 3 adjuvant, a universal PADRE T-helper epitope, and specific linkers to guarantee appropriate epitope presentation. The construct underwent thorough in silico validation, which encompassed physicochemical analysis, tertiary structure modeling, molecular docking with Toll-like receptor 4 (TLR4), MHC-I, and MHC-II molecules, molecular dynamics (MD) simulation, and an immune simulation based on agents. The completed vaccine construct, consisting of 291 amino acids, is expected to be a stable protein (Instability Index: 35.42) that is soluble, non-allergenic, and exhibits high antigenicity. Molecular docking simulations indicated a high binding affinity to crucial immune receptors, especially TLR4, showing a HADDOCK score of -42.2 6.2. MD simulations of the vaccine-TLR4 complex verified its dynamic stability over time. In addition, agent-based immune simulations forecasted the development of a strong, enduring, and well- regulated immune response, marked by elevated levels of class-switched immunoglobulins and the formation of substantial T-cell memory populations. The vaccine composed of multiple epitopes, developed and confirmed through this thorough in silico approach, stands as a hopeful and immunologically robust option for preventing CHIKV infection. These computational results provide robust support for advancing it into phases of experimental validation. Bioinformatics Vaccine Development Immunology Chikungunya Virus (CHIKV) Reverse Vaccinology Multi-Epitope Vaccine Immunoinformatics Beta-defensin 3 Molecular Docking Molecular Dynamics Simulation Immune Simulation Full Text Additional Declarations The authors declare no competing interests. Supplementary Files Bcellepitopes.xlsx ClonedDNASEQUENCE.gbk MHC1Q8JUX5.xlsx MHCIIQ8JUX5.xlsx 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. 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