Post-pandemic memory T cell response to SARS-CoV-2 is durable, broadly targeted, and cross-reactive to the hypermutated BA.2.86 variant
Rofhiwa Nesamari, Millicent A. Omondi, Richard Baguma, Maxine A. Höft, Amkele Ngomti, Anathi A. Nkayi, Asiphe S. Besethi, Siyabulela F. J. Magugu, Paballo Mosala, Avril Walters, G Clark, Mathilda Mennen, Sango Skelem, Marguerite Adriaanse, Alba Grifoni, Alessandro Sette, Roanne Keeton, Ntobeko Ntusi, Catherine Riou, Wendy A. Burgers
Abstract
Ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has given rise to recombinant Omicron lineages that dominate globally (XBB.1), as well as the emergence of hypermutated variants (BA.2.86). In this context, durable and cross-reactive T cell immune memory is critical for continued protection against severe COVID-19. We examined T cell responses to SARS-CoV-2 approximately 1.5 years since Omicron first emerged. We describe sustained CD4+ and CD8+ spike-specific T cell memory responses in healthcare workers in South Africa (n = 39) who were vaccinated and experienced at least one SARS-CoV-2 infection. Spike-specific T cells are highly cross-reactive with all Omicron variants tested, including BA.2.86. Abundant nucleocapsid and membrane-specific T cells are detectable in most participants. The bulk of SARS-CoV-2-specific T cell responses have an early-differentiated phenotype, explaining their persistent nature. Overall, hybrid immunity leads to the accumulation of spike and non-spike T cells evident 3.5 years after the start of the pandemic, with preserved recognition of highly mutated SARS-CoV-2 variants.