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Profiling CD8⁺ T cell epitopes of COVID-19 convalescents reveals reduced cellular immune responses to SARS-CoV-2 variants.

ABSTRACT: Cellular immunity is important in determining the disease severity of COVID-19 patients. However, current understanding of SARS-CoV-2 epitopes mediating cellular immunity is limited. Here we apply T-Scan, a recently developed method, to identify CD8⁺ T cell epitopes from COVID-19 patients of four major HLA-A alleles. Several identified epitopes are conserved across human coronaviruses, which might mediate pre-existing cellular immunity to SARS-CoV-2. In addition, we identify and validate four epitopes that were mutated in the newly circulating variants, including the Delta variant. The mutations significantly reduce T cell responses to the epitope peptides in convalescent and vaccinated samples. We further determine the crystal structure of HLA-A^∗02:01/HLA-A^∗24:02 in complex with the epitope KIA_S/NYN_S, respectively, which reveals the importance of K417 and L452 of the spike protein for binding to HLA. Our data suggest that evading cellular immunity might contribute to the increased transmissibility and disease severity associated with the new SARS-CoV-2 variants.

SUBMITTER: Zhang H

PROVIDER: S-EPMC8390359 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Profiling CD8<sup>+</sup> T cell epitopes of COVID-19 convalescents reveals reduced cellular immune responses to SARS-CoV-2 variants.

Zhang Hang H Deng Shasha S Ren Liting L Zheng Peiyi P Hu Xiaowen X Jin Tengchuan T Tan Xu X

Cell reports 20210827 11

Cellular immunity is important in determining the disease severity of COVID-19 patients. However, current understanding of SARS-CoV-2 epitopes mediating cellular immunity is limited. Here we apply T-Scan, a recently developed method, to identify CD8<sup>+</sup> T cell epitopes from COVID-19 patients of four major HLA-A alleles. Several identified epitopes are conserved across human coronaviruses, which might mediate pre-existing cellular immunity to SARS-CoV-2. In addition, we identify and valid ...[more]

PMID: 34506741

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Project description: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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Profiling CD8⁺ T cell epitopes of COVID-19 convalescents reveals reduced cellular immune responses to SARS-CoV-2 variants.

Publications

Profiling CD8<sup>+</sup> T cell epitopes of COVID-19 convalescents reveals reduced cellular immune responses to SARS-CoV-2 variants.

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Profiling CD8+ T cell epitopes of COVID-19 convalescents reveals reduced cellular immune responses to SARS-CoV-2 variants.

Publications

Profiling CD8<sup>+</sup> T cell epitopes of COVID-19 convalescents reveals reduced cellular immune responses to SARS-CoV-2 variants.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Profiling CD8⁺ T cell epitopes of COVID-19 convalescents reveals reduced cellular immune responses to SARS-CoV-2 variants.