Seeing SARS-CoV-2 variants through the eyes of T cells

Abstract

A preprint by Tarke et al. suggests a neglible impact of SARS-CoV-2 variant mutations on T cell reactivity in convalescent individuals and mRNA vaccine recipients.

The recent emergence of new SARS-CoV-2 variants of concern, including the B.1.1.7 variant in the UK, B.1.351 variant in South Africa, P.1 variant in Brazil and B.1.427 variant in California, USA, has important implications for future responses to the pandemic. Whereas the effects of mutations in the viral spike (S) protein on antibody binding and neutralization have been addressed in several reports, the impact of SARS-CoV-2 variant mutations on T cell reactivity remains poorly understood.

In this non-peer-reviewed preprint, Tarke et al. applied an integrated approach to assess T cell responses to SARS-CoV-2 variants from 11 COVID-19 convalescent individuals and 19 recipients of the Moderna (mRNA-1273) or Pfizer/BioNTech (BNT162b2) vaccines. Different methodologies were used to detect T cells with a range of functionalities and specific cytokine activity in response to overlapping peptide pools spanning the S protein of the original SARS-CoV-2 sequence and each of the corresponding variants.

Both CD4⁺ and CD8⁺ T cells from COVID-19 convalescent donors were found to recognize the ancestral reference strain and the variant proteome-wide sequences with similar efficiency. In mRNA vaccine recipients also, CD4⁺ and CD8⁺ T cell responses to the ancestral and variant peptide pools were similar, with the exception of the B.1.351 variant, for which mildly decreased T cell reactivity to S protein peptides was observed. Analysis of defined T cell epitopes showed that 93% of CD4⁺ T cell epitopes and 97% of CD8⁺ T cell epitopes are conserved in the analysed variants. Single point mutations in the T cell epitopes were predicted to have no negative effect on HLA binding capacity, which provides a molecular basis for the marginal impact of the mutations on T cell responses in the study group.

Together, these findings suggest a negligible impact of the SARS-CoV-2 variant mutations on global CD4⁺ and CD8⁺ T cell responses in COVID-19 convalescent donors and COVID-19 mRNA vaccine recipients, and have important implications for the design of vaccines inducing broader immunity against variants of concern. The use of overlapping peptide pools in this study does not exclude the possibility that mutations described in the variants could interfere with antigen processing, thereby affecting T cell activation and function. It remains to be determined whether T cell responses following infection with circulating variants can efficiently cross-recognize the ancestral sequence in approved vaccines.