SARS-CoV-2 Omicron BA.4/BA.5 Mutations in Spike Leading to T Cell Escape in Recently Vaccinated Individuals

• Published in: Viruses Vol. 15; no. 1; p. 101
• Main Authors: Emmelot, Maarten E., Vos, Martijn, Boer, Mardi C., Rots, Nynke Y., van Els, Cécile A. C. M., Kaaijk, Patricia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.12.2022; MDPI
• Subjects: Antibodies, Neutralizing; Antibodies, Viral; bioinformatics; BNT162 Vaccine; CD4 antigen; COVID-19 - prevention & control; COVID-19 Vaccines; cross reaction; Cross-reactivity; Epitopes; Epitopes, T-Lymphocyte - genetics; Flow cytometry; Histocompatibility antigen HLA; Humans; Lymphocytes; Lymphocytes T; mRNA; mRNA vaccines; Mutation; mutations; Omicron BA.1 variant; Omicron BA.4/BA.5 variants; Peptides; Proteins; SARS-CoV-2; SARS-CoV-2 - genetics; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - genetics; T cell response; T-Lymphocytes; vaccination; Vaccines; United States > US; Switzerland; Europe; Germany; SARS-CoV-2; HLA motif prediction; mutations; T cell response; CD4+ T cell epitopes; Omicron BA.1 variant; cross-reactivity; immune escape; Omicron BA.4/BA.5 variants; vaccination
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v15010101

SARS-CoV-2 Omicron (B.1.1.529) lineages rapidly became dominant in various countries reflecting its enhanced transmissibility and ability to escape neutralizing antibodies. Although T cells induced by ancestral SARS-CoV-2-based vaccines also recognize Omicron variants, we showed in our previous study that there was a marked loss of T cell cross-reactivity to spike epitopes harboring Omicron BA.1 mutations. The emerging BA.4/BA.5 subvariants carry other spike mutations than the BA.1 variant. The present study aims to investigate the impact of BA.4/BA.5 spike mutations on T cell cross-reactivity at the epitope level. Here, we focused on universal T-helper epitopes predicted to be presented by multiple common HLA class II molecules for broad population coverage. Fifteen universal T-helper epitopes of ancestral spike, which contain mutations in the Omicron BA.4/BA.5 variants, were identified utilizing a bioinformatic tool. T cells isolated from 10 subjects, who were recently vaccinated with mRNA-based BNT162b2, were tested for functional cross-reactivity between epitopes of ancestral SARS-CoV-2 spike and the Omicron BA.4/BA.5 spike counterparts. Reduced T cell cross-reactivity in one or more vaccinees was observed against 87% of the tested 15 non-conserved CD4+ T cell epitopes. These results should be considered for vaccine boosting strategies to protect against Omicron BA.4/BA.5 and future SARS-CoV-2 variants.