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

Viruses. 2022 Dec 29;15(1):101. doi: 10.3390/v15010101.

Abstract

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.

Keywords: CD4+ T cell epitopes; HLA motif prediction; Omicron BA.1 variant; Omicron BA.4/BA.5 variants; SARS-CoV-2; T cell response; cross-reactivity; immune escape; mutations; vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • BNT162 Vaccine*
  • COVID-19 Vaccines
  • COVID-19* / prevention & control
  • Epitopes, T-Lymphocyte / genetics
  • Humans
  • Mutation
  • SARS-CoV-2 / genetics
  • Spike Glycoprotein, Coronavirus / genetics
  • T-Lymphocytes

Substances

  • BNT162 Vaccine
  • Antibodies, Neutralizing
  • COVID-19 Vaccines
  • Epitopes, T-Lymphocyte
  • Spike Glycoprotein, Coronavirus
  • Antibodies, Viral
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants

Grants and funding

This work was supported by the Dutch Ministry of Health, Welfare and Sport.