Background
The novel coronavirus disease (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to the ongoing 2019-2020 pandemic. SARS-CoV-2 is a positive-sense single-stranded RNA coronavirus. Effective countermeasures against SARS-CoV-2 infection require the design and development of specific and effective vaccine candidates.
Objective
To address the urgent need for a SARS-CoV-2 vaccine, in the present study, we designed and validated one cytotoxic T lymphocyte (CTL) and one helper T lymphocyte (HTL) multi-epitope vaccine (MEV) against SARS-CoV-2 using various in silico methods.
Methods
Both designed MEVs are composed of CTL and HTL epitopes screened from 11 structural and nonstructural proteins of the SARS-CoV-2 proteome. Both MEVs also carry potential B-cell linear and discontinuous epitopes as well as interferon gamma–inducing epitopes. To enhance the immune response of our vaccine design, truncated (residues 10-153) Onchocerca volvulus activation-associated secreted protein-1 was used as an adjuvant at the N termini of both MEVs. The tertiary models for both the designed MEVs were generated, refined, and further analyzed for stable molecular interaction with toll-like receptor 3. Codon-biased complementary DNA (cDNA) was generated for both MEVs and analyzed in silico for high level expression in a mammalian (human) host cell line.
Results
In the present study, we screened and shortlisted 38 CTL, 33 HTL, and 12 B cell epitopes from the 11 protein sequences of the SARS-CoV-2 proteome. Moreover, the molecular interactions of the screened epitopes with their respective human leukocyte antigen allele binders and the transporter associated with antigen processing (TAP) complex were positively validated. The shortlisted screened epitopes were utilized to design two novel MEVs against SARS-CoV-2. Further molecular models of both MEVs were prepared, and their stable molecular interactions with toll-like receptor 3 were positively validated. The codon-optimized cDNAs of both MEVs were also positively analyzed for high levels of overexpression in a human cell line.
Conclusions
The present study is highly significant in terms of the molecular design of prospective CTL and HTL vaccines against SARS-CoV-2 infection with potential to elicit cellular and humoral immune responses. The epitopes of the designed MEVs are predicted to cover the large human population worldwide (96.10%). Hence, both designed MEVs could be tried in vivo as potential vaccine candidates against SARS-CoV-2.
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
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