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

Abstract

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.

A Synthetic SARS-CoV-2-Derived T-Cell and B-Cell Peptide Cocktail Elicits Full Protection against Lethal Omicron BA.1 Infection in H11-K18-hACE2 Mice

“…Common HLA allotypes can be selected using computational techniques and bioinformatics resources, such as the SYFPEITHI and NetMHCpan ( 60 – 63 ) algorithms, and mutation-prone regions should be removed. Many functional SARS-CoV-2-derived T-cell epitopes have been identified and require further experimental validation ( 64 – 66 ). For effective B-cell epitope selection, the three-dimensional structure of the epitope is crucial.…”

Harnessing immunoinformatics for developing a multiple-epitope peptide-based vaccination approach against SARS-CoV-2 spike protein

“…However, the emergence of variants like Delta, Gamma, Beta, and Omicron, left the globe vigilant towards COVID-19 ( Aasim and R., Patil, C. R., Kumar, A., & Sharma, K. , 2022 , Martin et al, 2021 ). The presently S protein-based vaccines not only failed to prevent transmission of the virus but might also had a role in selection of new variants like omicron( Palatnik-de-Sousa et al, 2022 ), that has around 30 mutations in SARS-CoV-2 S protein, which enhance receptors binding process as well as virus transmission. The importance of the S protein lies in its involvement in entry and membrane merging of the virus into host cells ( Hwang et al, 2020 ).…”

Emergency Protective Measures and Strategies of COVID-19: From Lifestyle to Traditional Chinese Medicine

“…Herein, they can lead a happy life at home during the pandemics. Clearly, this lifestyle is effective for control and prevention of Omicron infection, which has high infectivity due to an increased transmission and immune escape ( Liu et al, 2022 ; Wang et al, 2022 ; Lee et al, 2022 ; He et al, 2022 ; Palatnik-de-Sousa et al, 2022 ), since the rational isolation strategy covered the SARS-CoV-2 incubating period of 7-14 days. Thus, people can fight the epidemic more effectively while ensuring the quality of life in the new era.…”