AUTHOR=Lopes-Ribeiro Ágata , Oliveira Patrícia de Melo , Retes Henrique Morais , Barbosa-Stancioli Edel Figueiredo , da Fonseca Flávio Guimarães , Tsuji Moriya , Coelho-dos-Reis Jordana Grazziela Alves TITLE=Surveillance of SARS-CoV-2 immunogenicity: loss of immunodominant HLA-A*02-restricted epitopes that activate CD8+ T cells JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1229712 DOI=10.3389/fimmu.2023.1229712 ISSN=1664-3224 ABSTRACT=Introduction and methods

In this present work, coronavirus subfamilies and SARS-CoV-2 Variants of Concern (VOCs) were investigated for the presence of MHC-I immunodominant viral peptides using in silico and in vitro tools.

Results

In our results, HLA-A*02 haplotype showed the highest number of immunodominant epitopes but with the lowest combined prediction score. Furthermore, a decrease in combined prediction score was observed for HLA-A*02-restricted epitopes when the original strain was compared to the VOCs, indicating that the mutations on the VOCs are promoting escape from HLA-A2-mediated antigen presentation, which characterizes a immune evasion process. Additionally, epitope signature analysis revealed major immunogenic peptide loss for structural (S) and non-structural (ORF8) proteins of VOCs in comparison to the Wuhan sequence.

Discussion

These results may indicate that the antiviral CD8+ T-cell responses generated by original strains could not be sufficient for clearance of variants in either newly or reinfection with SARS-CoV-2. In contrast, N epitopes remain the most conserved and reactive peptides across SARS-CoV-2 VOCs. Overall, our data could contribute to the rational design and development of new vaccinal platforms to induce a broad cellular CD8+ T cell antiviral response, aiming at controlling viral transmission of future SARS-CoV-2 variants.