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

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.
Competing Interests: Declaration of interests A.S. is a consultant for AstraZeneca Pharmaceuticals; Calyptus Pharmaceuticals, Inc; Darwin Health; EmerVax; EUROIMMUN; F. Hoffman-La Roche Ltd; Fortress Biotech; Gilead Sciences; Granite Bio.; Gritstone Oncology; Guggenheim Securities; Moderna; Pfizer; RiverVest Venture Partners; and Turnstone Biologics. A.G. is a consultant for Pfizer. A.S. has filed for patent protection for various aspects of T cell epitope and vaccine design work. M.B. is a consultant and has received honoraria from Oxford Immunotec, MSD, BMS, Pfizer, and Mabtech. S.A. has received honoraria for lectures and educational events, not related to this work, from Gilead, AbbVie, MSD, and Biogen and reports grants from Gilead and AbbVie.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)