Immunoinformatic Responses of Host MHC I/II and CD4+ Cells Against Conserved Spike Fragments of SARS CoV-2 of 186 Countries With In-Silico Mutations: Implications in Universal Vaccination

Different types of quickly-developed vaccines have been introduced against Covid-19 with largely inconclusive results. On the course of time, somewhere Covid-19 declines its infection/mortality rate and in some countries it revived with some new mutant-variants. Considering the large number of global variants, in the current study several conserved (186 countries) sequences (checked by ClustalX2) epitopic regions (by SVMTriP and IEDB) and in-silico mutants of SARS CoV-2 spike protein fragments (Cut 1-4) were screened for their stability against proteases, antigenicity (VaxiJen V2.0 and for glycosylation effects NetOGlyc-NetNGlyc), MHCI/II reactivity (IEDB TOOLS) and CD4+ cellular responses utilizing Haddock 2.4 and PatchDock programme. The cut4 mutant and its peptide SRLFRKSNLKPFERD showed highest combined-score 48.23548 and Immunogenicity-Score of 92.0887. The core-sequence SRLFRKSNL showed highest Median Percentile Rank (7 HLA-allele) of 19. CD4+ immunogenicity also confirms representation of CUT4TM2 epitope SRLFRKSNL by MHC Class II. The epitope YNYKYRLFR from CUT4 showed IC50 value of ~30 nM with allele HLA-DRB1*11:01 and HLA-DRB5*01:01. Binding affinity and RMSD score suggest that different epitopic regions of Cut4 mutants interacted MHC II with large number of H-bonds. Cut4 double mutants strongly interacted with exposed T-cell surface and facilitated by its receptors. According to the antigenicity analysis, epitopes 3, 4, and 5 were the potent antigens with antigenicity values of 0.6268, 1.2404, and 0.4639, respectively. Screening of conserved SARS CoV-2 spike fragments globally may help to find most stable antigenic determinant and further their mutation-engendered counterparts have better immunogenic responses. Further studies are necessary to develop global vaccination strategies against Covid-19.