Structural basis of development of multi-epitope vaccine against Middle East respiratory syndrome using in silico approach

Abstract

BackgroundMiddle East respiratory syndrome (MERS) is caused by MERS coronavirus (MERS-CoV). Thus far, MERS outbreaks have been reported from Saudi Arabia (2013 and 2014) and South Korea (2015). No specific vaccine has yet been reported against MERS.PurposeTo address the urgent need for an MERS vaccine, in the present study, we have designed two multi-epitope vaccines (MEVs) against MERS utilizing several in silico methods and tools.MethodsThe design of both the multi-epitope vaccines (MEVs) are composed of cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) epitopes, screened form thirteen different proteins of MERS-CoV. Both the MEVs also carry potential B-cell linear epitope regions, B-cell discontinuous epitopes as well as interferon-γ-inducing epitopes. Human β-defensin-2 and β-defensin-3 were used as adjuvants to enhance the immune response of MEVs. To design the MEVs, short peptide molecular linkers were utilized to link screened most potential CTL epitopes, HTL epitopes and the adjuvants. Tertiary models for both the MEVs were generated, refined, and further studied for their molecular interaction with toll-like receptor 3. The cDNAs of both MEVs were generated and analyzed in silico for their expression in a mammalian host cell line (human).ResultsScreened CTL and HTL epitopes were found to have high propensity for stable molecular interaction with HLA alleles molecules. CTL epitopes were also found to have favorable molecular interaction within the cavity of transporter associated with antigen processing. The selected CTL and HTL epitopes jointly cover upto 94.0% of worldwide human population. Both the CTL and HTL MEVs molecular models have shown to have stable binding and complex formation propensity with toll-like receptor 3. The cDNA analysis of both the MEVs have shown high expression tendency in mammalian host cell line (human).ConclusionAfter multistage in silico analysis, both the MEVs are predicted to elicit humoral as well as cell mediated immune response. Epitopes of the designed MEVs are predicted to cover large human population worldwide. Hence both the designed MEVs could be tried in vivo as potential vaccine candidates against MERS.

Design an efficient multi-epitope peptide vaccine candidate against SARS-CoV-2: An in silico analysis

“…This is a potent immune adjuvant for inducing cellular and humoral immune responses and used in vaccines against viral infection such as HIV and HPV [84-87]. HBD-3 is the third adjuvant in our vaccine, used as adjuvant to viruses such as influenza and MERS-CoV [26, 88]. This peptide blocks viral fusion using creating a protective barricade of immobilized surface proteins[88].…”

“…Bioinformatic approaches are very helpful to identify the effective epitopes and developing vaccine. Several vaccines for virus diseases were designed based on these approaches that include effective vaccines on Human papilloma viridea (HPV) [23],Ebola [24], Zika[25]and MERS[26, 27]viruses. There are also few reports of a vaccine candidate for COVID19[28, 29].…”

Scouting the Receptor Binding Domain of COVID-19: A Comprehensive Immunoinformatics Inquisition

“…A comprehensive immunoinformatics data mining of RBD can increase our understanding for its antigenic profile. Encouragingly, epitope prediction analysis were reported earlier for SARS and MERS strains [22,19] and quite recently for COVID-19 [23][24][25].…”

Coronavirus Pandemic—Therapy and Vaccines

“…These identified putative antigenic epitopes may prove effective for the development of novel vaccines. Using in silico approaches, two multi-epitope vaccines against MERS-CoV were designed by screening CTL and HTL epitopes from 13 different MERS-CoV proteins [137]. Both multi-epitope vaccines also carried potential B cell linear epitope regions, B cell discontinuous epitopes and interferon-γ-inducing epitopes.…”