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

Abstract

The COVID-19 pandemic caused by SARS-CoV-2 is a public-health emergency of international concern and thus calling for the development of safe and effective therapeutics and prophylactics particularly a vaccine to protect against the infection. SARS-CoV-2 spike glycoprotein is an attractive candidate for vaccine, antibodies and inhibitor development because of many roles it plays in attachment, fusion and entry into the host cell. In this study, we characterized the SARS-CoV-2 spike glycoprotein by immune-informatics techniques to put forward potential B and T cell epitopes, followed by the use of epitopes in construction of a multi-epitope peptide vaccine construct (MEPVC). The MEPVC revealed robust host immune system simulation with high production of immunoglobulins, cytokines and interleukins. Stable conformation of the MEPVC with a representative innate immune TLR3 receptor was observed involving strong hydrophobic and hydrophilic chemical interactions, along with enhanced contribution from salt-bridges towards inter-molecular stability. Molecular dynamics simulation in solution aided further in interpreting strong affinity of the MEPVC for TLR3. This stability is the attribute of several vital residues from both TLR3 and MEPVC as shown by radial distribution function (RDF) and a novel analytical tool axial frequency distribution (AFD). Comprehensive binding free energies estimation was provided at the end that concluded major domination by electrostatic and minor from van der Waals. Summing all, the designed MEPVC has tremendous potential of providing protective immunity against COVID-19 and thus has the potential to be considered in experimental studies.

Multiepitope-Based Subunit Vaccine Design and Evaluation against Respiratory Syncytial Virus Using Reverse Vaccinology Approach

“…The final vaccine is moderately basic and can give a stable connection in the physiological pH range. The mean half-life of the construct was calculated as 30 h in vitro, >20 h in vivo and >0 h in yeast, which is consistent with already reported subunit vaccine studies [22,51,52,82,83,107]. Furthermore, results disclosed the vaccine as thermostable while the negative GRAVY recommended its hydrophilicity, proposing strong connections towards water molecules.…”

“…Clinically the minimum recommended interval between two doses of vaccines is four weeks [52,[79][80][81]. Immune simulation was performed using the similar protocol reported by earlier studies [51,52,80,82,83]. Briefly, three injections were administered with the recommended intervals of four weeks (1, 84 and 168 time-steps parameters were set, as one time-step is equal to eight hours of real life) for a total of 1050 steps of simulation.…”

Computationally Optimized SARS-CoV-2 MHC Class I and II Vaccine Formulations Predicted to Target Human Haplotype Distributions

“…We used EvalVax to evaluate peptide vaccines and megapools proposed by other publications ( Lee and Koohy, 2020 ; Fast et al., 2020 ; Poran et al., 2020 ; Bhattacharya et al., 2020 ; Baruah and Bose, 2020 ; Abdelmageed et al., 2020 ; Ahmed et al., 2020 ; Srivastava et al., 2020 ; Herst et al., 2020 ; Vashi et al., 2020 ; Akhand et al., 2020 ; Mitra et al., 2020 ; Khan et al., 2020 ; Banerjee et al., 2020 ; Ramaiah and Arumugaswami, 2020 ; Gupta et al., 2020 ; Saha and Prasad, 2020 ; Tahir ul Qamar et al, 2020 ; Singh et al., 2020 ; Yarmarkovich et al., 2020 ; Grifoni et al., 2020a ; Nerli and Sgourakis, 2020 ; Yazdani et al., 2020 ; Ismail et al., 2020 ) on metrics including EvalVax-Unlinked and EvalVax-Robust population coverage at different per-individual number of peptide-HLA hits thresholds, expected per-individual number of peptide-HLA hits in White, Black, and Asian populations, percentage of peptides that are predicted to be glycosylated, peptides observed to mutate with a probability greater than 0.001, or peptides that sit on known cleavage sites. We define “normalized coverage” as the mean expected per-individual number of peptide-HLA hits for a vaccine divided by the number of peptides in the vaccine.…”

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

“…On the other hand, the multi-epitope vaccine involves fusion of multiple epitopes identified from the proteome of the SARS-CoV-2 by short peptide linkers. Several subunit and multi-epitope-based vaccine designs have been published claiming potential to activate CD4 and CD8 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 & Bose, 2020 ; Bhattacharya et al, 2020 ; Fast & Chen, 2020 ; Gragert et al, 2013 ; Gupta et al, 2020 ; Herst et al, 2020 ; Ismail et al, 2020 ; Khan et al, 2020 ; Lee & Koohy, 2020 ; Liu et al, 2020 ; Lu et al, 2014 ; Mitra et al, 2020 ; Nerli & Sgourakis, 2020 ; Poran et al, 2020 ; Ramaiah & Arumugaswami, 2020 ; Saha & Prasad, 2020 ; Sheikhshahrokh et al, 2020 ; Singh et al, 2020 ; Srivastava et al, 2020a ; 2020b ; Ul Qamar et al, 2020 ; Vashi et al, 2020 ; Yarmarkovich, Farrel et al, 2020; Yazdani et al, 2020 ). Numerous highly antigenic regions have also been reported from SARS-CoV-2 proteins, which have been recognized with a large population coverage by favorable binding with large number of HLA allele distributed among different ethnic human population across the world (Grifoni et al, 2020b ; Yarmarkovich, Warrington, et al, 2020 ).…”