Structural basis to design multi-epitope vaccines against Novel Coronavirus 19 (COVID19) infection, the ongoing pandemic emergency: an in silico approach

Abstract

31The 2019 novel coronavirus (COVID19 / Wuhan coronavirus), officially named as 32Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a positive-33 sense single-stranded RNA coronavirus. SARS-CoV-2 causes the contagious 34 was not certified by peer review) measures against SARS-CoV-2 infection require the design and development of 37 specific and effective vaccine candidate. In the present study, we have screened 38 and shortlisted 38 CTL, 33 HTL and 12 B cell epitopes from the eleven Protein 39 sequences of SARS-CoV-2 by utilizing different in silico tools. The screened 40 epitopes were further validated for their binding with their respective HLA allele 41 binders and TAP (Transporter associated with antigen processing) molecule by 42 molecular docking. The shortlisted screened epitopes were further utilized to 43 design novel two multi-epitope vaccines (MEVs) composed of CTL, HTL and B 44 cell epitopes overlaps with potential to elicit humoral as well as cellular immune 45 response against SARS-CoV-2. To enhance the immune response for our 46 vaccine design, truncated (residues 10-153) Onchocerca volvulus activation-47 associated secreted protein-1 (Ov-ASP-1) has been utilized as an adjuvant at N 48 terminal of both the MEVs. Further molecular models for both the MEVs were 49 prepared and validated for their stable molecular interactions with Toll-Like 50 Receptor 3 (TLR 3). The codon-optimized cDNA of both the MEVs were further 51 analyzed for their potential of high level of expression in a human cell line. The 52 present study is very significant in terms of molecular designing of prospective 53 CTL and HTL vaccine against SARS-CoV-2 infection with the potential to elicit 54 cellular as well as humoral immune response. 55 56

De novo design of high-affinity antibody variable regions (Fv) against the SARS-CoV-2 spike protein

“…At the same time, significant progress towards the isolation and design of vaccines (mRNA-1273 vaccine © 2020 Moderna, Inc) and neutralizing antibodies 9 has been made. A computational study identified the structural basis for multi-epitope vaccines 10,11 whereas in another study, the glycosylation patterns of the spike SARS-CoV-2 protein were computationally deduced 12 . In one study 13 , fully human single domain anti-SARS-CoV-2 antibodies with sub-nanomolar affinities were identified from a phage-displayed single-domain antibody library by grafting naïve CDRs into framework regions of an identified human germline IGHV allele using SARS-CoV-2 RBD and S1 protein as antigens.…”

Computationally validated SARS-CoV-2 CTL and HTL Multi-Patch Vaccines designed by reverse epitomics approach, shows potential to cover large ethnically distributed human population worldwide

“…The identified Ag-Patches were highly conserved in nature and were identified on the basis of significant number of overlapping epitope forming clusters (Figure 2, 3 & 4). Ag-Patches together, and to facilitate folding of the protein into its tertiary conformation (Hu et al, 2004;Wilson et al, 2013;Duits et al, 2003;Chen et al, 2013;Hajighahramani et al, 2017;Srivastava et al, 2019;Srivastava et al, 2018;Srivastava et al, 2020a;Srivastava et al, 2020b) ( Figure 1A, 1B, 2 (Table 3). from CTL-MPV-3); likewise, a total of IFN-γ inducing epitopes were screened from two HTL MPVs (83 from HTL-MPV-1 and 98 from HTL-MPV-2).…”

“…All the three CTL and two HTL MPVs were fitting into the ectodomain region of TLR3 receptor (Figure 7). T cell immune response driving long-term robust adaptive immunity in the vast majority of the population (Abdelmageed et al, 2020;Ahmed et al, 2020;Akhand et al, 2020;An et al, 2000;Banerjee et al, 2020;Baruah et al, 2020;Bhattacharya et al, 2020;Fast et al, 2020;Gragert et al, 2013;Gupta et al, 2020;Herst et al, 2020;Ismail et al, 2020;Khan et al, 2020;Lee et al, 2020;Liu et al, 2020;Lu et al, 2014;Mitra et al, 2020;Nerli et al, 2020;Poran et al, 2020;Ramaiah et al, 2020;Saha et al, 2020;Sheikhshahrokh et al, 2020;Singh et al, 2020;Srivastava et al, 2020a;Srivastava et al, 2020b;ul Qamar et al, 2020;Vashi et al, 2020;Yazdani et al, 2020). Numerous highly antigenic regions have also been reported from SARS-CoV-2 proteins which have been recognized on the basis of large population coverage by favorable binding with large number of HLA allele distributed amongst different ethnic human population worldwide (Grifoni et al, 2020b;Yarmarkovich and Warrington et al, 2020).…”

“…The proteasome and lysosomal chop down processing of MPVs by the Antigen Presenting cells would release larger number of epitopes in their intact form for which the MEVs would have a challenge. Moreover the Ag-Patch based MPVs will cover larger number of overlapping epitopes in comparison to the limited number of epitopes covered by epitope based MEVs (Srivastava et al, 2020a;Srivastava et al, 2020b). The larger the number of epitopes covered larger would be the number of HLA alleles targeted and hence larger human population with ethnic distribution of HLA alleles will be covered.…”

“…The immunogenicity analysis of all the screened CTL epitopes was also performed by the tool "MHC I Immunogenicity" of IEDB. The higher immunogenicity score of all the screened CTL epitopes suggest the high immunogenic potential of the CTL epitopes (Supplementary table S1, S2;Srivastava et al 2020a;Srivastava et al 2020b;and Grifoni et al, 2020a). MHC-II Binding Predictions" tool of IEDB.…”