Engineering a multi epitope vaccine against SARS-CoV-2 by exploiting its non structural and structural proteins

Rajput, Vikrant Singh; Sharma, Ranjana; Kumari, Anchala; Vyas, Nidhi; Prajapati, Vijay Kumar; Grover, Abhinav

doi:10.1080/07391102.2021.1924265

Cited by 5 publications

(1 citation statement)

References 92 publications

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“…The IFN‐γ level was high and almost similar at all exposures. This tells us that the vaccine candidate developed in this study elicited a robust immune response at first injection, which was consequently increased (Shepard et al 1978 ; Rajput, et al 2021 ; Singh, et al 2020 ) (Fig. 5 ).…”

Section: Resultsmentioning

confidence: 65%

Multi-pathogen based chimeric vaccine to fight against COVID-19 and concomitant coinfections

et al. 2023

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Background COVID-19 has proved to be a fatal disease of the year 2020, due to which thousands of people globally have lost their lives, and still, the infection cases are at a high rate. Experimental studies suggested that SARS-CoV-2 interacts with various microorganisms, and this coinfection is accountable for the augmentation of infection severity. Methods and results In this study, we have designed a multi-pathogen vaccine by involving the immunogenic proteins from S. pneumonia, H. influenza, and M. tuberculosis , as they are dominantly associated with SARS-CoV-2. A total of 8 antigenic protein sequences were selected to predict B-cell, HTL, and CTL epitopes restricted to the most prevalent HLA alleles. The selected epitopes were antigenic, non-allergenic, and non-toxic and were linked with adjuvant and linkers to make the vaccine protein more immunogenic, stable, and flexible. The tertiary structure, Ramachandran plot, and discontinuous B-cell epitopes were predicted. Docking and MD simulation study has shown efficient binding of the chimeric vaccine with the TLR4 receptor. Conclusion The in silico immune simulation analysis has shown a high level of cytokines and IgG after a three-dose injection. Hence, this strategy could be a better way to decrease the disease's severity and could be used as a weapon to prevent this pandemic. Supplementary Information The online version contains supplementary material available at 10.1007/s10529-023-03380-0.

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Section: Resultsmentioning

confidence: 65%

Multi-pathogen based chimeric vaccine to fight against COVID-19 and concomitant coinfections

et al. 2023

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Screening HLA-A-restricted T cell epitopes of SARS-CoV-2 and the induction of CD8+ T cell responses in HLA-A transgenic mice

et al. 2021

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Since severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific T cells have been found to play essential roles in host immune protection and pathology in patients with coronavirus disease 2019 (COVID-19), this study focused on the functional validation of T cell epitopes and the development of vaccines that induce specific T cell responses. A total of 120 CD8+ T cell epitopes from the E, M, N, S, and RdRp proteins were functionally validated. Among these, 110, 15, 6, 14, and 12 epitopes were highly homologous with SARS-CoV, OC43, NL63, HKU1, and 229E, respectively; in addition, four epitopes from the S protein displayed one amino acid that was distinct from the current SARS-CoV-2 variants. Then, 31 epitopes restricted by the HLA-A2 molecule were used to generate peptide cocktail vaccines in combination with Poly(I:C), R848 or poly (lactic-co-glycolic acid) nanoparticles, and these vaccines elicited robust and specific CD8+ T cell responses in HLA-A2/DR1 transgenic mice as well as wild-type mice. In contrast to previous research, this study established a modified DC-peptide-PBL cell coculture system using healthy donor PBMCs to validate the in silico predicted epitopes, provided an epitope library restricted by nine of the most prevalent HLA-A allotypes covering broad Asian populations, and identified the HLA-A restrictions of these validated epitopes using competitive peptide binding experiments with HMy2.CIR cell lines expressing the indicated HLA-A allotype, which initially confirmed the in vivo feasibility of 9- or 10-mer peptide cocktail vaccines against SARS-CoV-2. These data will facilitate the design and development of vaccines that induce antiviral CD8+ T cell responses in COVID-19 patients.

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A novel vaccine based on SARS-CoV-2 CD4+ and CD8+ T cell conserved epitopes from variants Alpha to Omicron

Palatnik-de-Sousa

Wallace

Cavalcante

et al. 2022

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COVID-19 caused, as of September, 1rst, 2022, 599,825,400 confirmed cases, including 6,469,458 deaths. Currently used vaccines reduced severity and mortality but not virus transmission or reinfection by different strains. They are based on the Spike protein of the Wuhan reference virus, which although highly antigenic suffered many mutations in SARS-CoV-2 variants, escaping vaccine-generated immune responses. Multiepitope vaccines based on 100% conserved epitopes of multiple proteins of all SARS-CoV-2 variants, rather than a single highly mutating antigen, could offer more long-lasting protection. In this study, a multiepitope multivariant vaccine was designed using immunoinformatics and in silico approaches. It is composed of highly promiscuous and strong HLA binding CD4+ and CD8+ T cell epitopes of the S, M, N, E, ORF1ab, ORF 6 and ORF8 proteins. Based on the analysis of one genome per WHO clade, the epitopes were 100% conserved among the Wuhan-Hu1, Alpha, Beta, Gamma, Delta, Omicron, Mµ, Zeta, Lambda and R1 variants. An extended epitope-conservancy analysis performed using GISAID metadata of 3,630,666 SARS-CoV-2 genomes of these variants and the additional genomes of the Epsilon, Lota, Theta, Eta, Kappa and GH490 R clades, confirmed the high conservancy of the epitopes. All but one of the CD4 peptides showed a level of conservation greater than 97% among all genomes. All but one of the CD8 epitopes showed a level of conservation greater than 96% among all genomes, with the vast majority greater than 99%. A multiepitope and multivariant recombinant vaccine was designed and it was stable, mildly hydrophobic and non-toxic. The vaccine has good molecular docking with TLR4 and promoted, without adjuvant, strong B and Th1 memory immune responses and secretion of high levels of IL-2, IFN-γ, lower levels of IL-12, TGF-β and IL-10, and no IL-6. Experimental in vivo studies should validate the vaccine’s further use as preventive tool with cross-protective properties.

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Engineering a multi epitope vaccine against SARS-CoV-2 by exploiting its non structural and structural proteins

Cited by 5 publications

References 92 publications

Multi-pathogen based chimeric vaccine to fight against COVID-19 and concomitant coinfections

Multi-pathogen based chimeric vaccine to fight against COVID-19 and concomitant coinfections

Screening HLA-A-restricted T cell epitopes of SARS-CoV-2 and the induction of CD8+ T cell responses in HLA-A transgenic mice

A novel vaccine based on SARS-CoV-2 CD4+ and CD8+ T cell conserved epitopes from variants Alpha to Omicron

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