Accepted for/Published in: JMIR Bioinformatics and Biotechnology
Date Submitted: Apr 15, 2020
Date Accepted: May 27, 2020
Date Submitted to PubMed: May 28, 2020
Structural basis for designing multi-epitope vaccines against novel coronavirus 19 infection, the ongoing pandemic emergency: an in silico approach
ABSTRACT
Background:
The 2019 novel coronavirus (COVID19 / Wuhan coronavirus), officially named as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a positive-sense single-stranded RNA coronavirus. SARS-CoV-2 causes the contagious COVID19 disease also known as 2019-nCoV acute respiratory disease and has led to the ongoing 2019–20 pandemic COVID19 outbreak. The effective counter measures against SARS-CoV-2 infection require the design and development of specific and effective vaccine candidate.
Objective:
To address the urgent need for SARS-CoV-2 vaccine, in the present study, we have designed and validated one CTL and one HTL multi-epitope vaccines (MEVs) against SARS-CoV-2 utilizing several in silico methods.
Methods:
The design of both the multi-epitope vaccines (MEVs) are composed of cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) epitopes, screened form eleven structural and non-structural proteins of SARS-CoV-2 proteome. Both the MEVs also carry potential B-cell linear and discontinuous epitopes as well as interferon-γ-inducing epitopes. To enhance the immune response for our vaccine design, truncated (residues 10-153) Onchocerca volvulus activation-associated secreted protein-1 (Ov-ASP-1) has been utilized as an adjuvant at N terminal of both the MEVs. The tertiary models for both the designed MEVs were generated, refined, and further analyzed for stable molecular interaction with toll-like receptor 3. The codon biased cDNAs for both the MEVs were generated and analyzed in silico for high level of overexpression in a mammalian host cell line (human).
Results:
In the present study, we have screened and shortlisted 38 CTL, 33 HTL and 12 B cell epitopes from the eleven protein sequences of SARS-CoV-2 proteome. The screened epitopes were further validated positively for their molecular interaction with their respective HLA allele binders and TAP (Transporter associated with antigen processing) molecule. The shortlisted screened epitopes were utilized to design novel two multi-epitope vaccines (MEVs) against SARS-CoV-2. Further molecular models for both the MEVs were prepared and validated positively for their stable molecular interactions with Toll-Like Receptor 3 (TLR 3). The codon-optimized cDNA of both the MEVs were also analyzed positively for high level of overexpression in a human cell line.
Conclusions:
The present study is very significant in terms of molecular designing of prospective CTL and HTL vaccine against SARS-CoV-2 infection with the potential to elicit cellular as well as humoral immune response. Epitopes of the designed MEVs are predicted to cover large human population worldwide (96.10%). Hence both the designed MEVs could be tried in vivo as potential vaccine candidates against SARS-CoV-2. Clinical Trial: Not applicable for the present study.
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