Memory T cells effectively recognize the SARS-CoV-2 hypermutated BA.2.86 variant

Cell Host Microbe. 2024 Feb 14;32(2):156-161.e3. doi: 10.1016/j.chom.2023.12.010. Epub 2024 Jan 10.

Abstract

T cells are critical in mediating the early control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection. However, it remains unknown whether memory T cells can effectively cross-recognize new SARS-CoV-2 variants with a broad array of mutations, such as the emergent hypermutated BA.2.86 variant. Here, we report in two separate cohorts, including healthy controls and individuals with chronic lymphocytic leukemia, that SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by prior infection or vaccination demonstrate resilient immune recognition of BA.2.86. In both cohorts, we found largely preserved SARS-CoV-2 spike-specific CD4+ and CD8+ T cell magnitudes against mutated spike epitopes of BA.2.86. Functional analysis confirmed that both cytokine expression and proliferative capacity of SARS-CoV-2 spike-specific T cells to BA.2.86-mutated spike epitopes are similarly sustained. In summary, our findings indicate that memory CD4+ and CD8+ T cells continue to provide cell-mediated immune recognition to highly mutated emerging variants such as BA.2.86.

Keywords: BA.1; BA.2.86; SARS-CoV-2; T cells; cellular immunity.

MeSH terms

  • Antibodies, Viral
  • CD8-Positive T-Lymphocytes
  • COVID-19*
  • Epitopes
  • Humans
  • Memory T Cells*
  • SARS-CoV-2 / genetics
  • Spike Glycoprotein, Coronavirus / genetics

Substances

  • Epitopes
  • Spike Glycoprotein, Coronavirus
  • Antibodies, Viral
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants