Immuno-informatics Characterization SARS-CoV-2 Spike Glycoprotein for Prioritization of Epitope based Multivalent Peptide Vaccine

Saba Ismail; Sajjad Ahmad; Syed Sikander Azam

The SARS-CoV-2 spike protein was targeted for MEPVC designing because of many filters it fulfilled required for a potential vaccine candidate. First, it does not share any significant homology to the human host and as such chances of autoimmune responses are negligible [78] . Second, the protein is also not found to have any sequence identity to the mouse proteome and thus accurate immunological findings can be deciphered from in vivo mice experimentations [79] . This spike protein only harbored one transmembrane helix ensuring the wet lab protein cloning and expression for antigen analysis easy [80] . Antigenicity is another factor that make this candidate highly suitable for vaccine designing as this allows efficient binding to the products of host immune system [81] . Further, this protein is strongly adhesive which makes it an excellent target for creation of adhesion based vaccine [82] . Lastly, all the sequences of SARS-CoV-2 spike protein are highly conserved thus a vaccine based on its sequence will be highly likely to have broad spectrum immunological implications [83] . Prioritization of potential epitopes for the SARS-CoV-2 spike protein commenced with the mapping of B-cell epitopes that predicted total of 34 epitopes of vary length ranging from one to 62 (S Table 1 ). The average score predicted for these B cell epitopes is 0.470, maximum (max) of 0.696 and minimum (min) of 0.188 (Fig.2) . Each Bcell epitope was then analyzed in MHC-1 alleles binding regions prediction [84] . The predicted epitopes were then screened and stringent criteria of lowest percentile score was used to choose the excellent binders. Afterward, the B cell epitopes were simultaneously run in MHC-II alleles binding [85] . Likewise MHC-I, reference set of MHC-II binding were: HLA-DRB4*01:01, HLA-DRB1*04:01, HLA-DRB1*04:05, HLA-DRB1*07:01, HLA-DRB1*09:01, HLA-DRB1*11:01, HLA-DRB1*03:01, HLA-DRB1*13:02, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB1*12:01, HLA-DRB3*02:02, HLA-DRB1*08:02, HLA-DRB1*01:01, and HLA-DRB5*01:01. The MHC-II predicted epitopes were also filtered on basis of percentile score and then cross checked with the selected MHC-I allele and those common in both classes were considered only which were 50 in numbers. The shortlisted common MHC-I and MHC-II epitopes then subjected to antigenicity check. In this check, ability of the filtered B-cell derived T-cell epitopes ability to evoke and bind to products of adaptive immunity. This yielded 38 epitopes all of which have strong ability to bind to the most prevalent DRB*0101 with average IC50 score of 35.6552, max of 98 and min of 0.89.The antigenic epitopes then underwent allergenicity check to discard allergic peptides that may cause allergic reactions [86] . This resulted into 31 epitopes. Non-toxic epitopes were 7 whereas 6 were IFN-gamma producer (Fig.3) . The set of epitopes obtained at different author/funder. All rights reserved. No reuse allowed without permission.