NGS-SA: Publications and pre-prints of our genomics surveillance work

T cell responses to SARS-CoV-2 spike cross-recognize Omicron

Authors: Keeton R, Tincho MB, Ngomti A, Baguma R, Benede N, Suzuki A, Khan K, Cele S, Bernstein M, Karim F, Madzorera SV, Moyo-Gwete T, Mennen M, Skelem S, Adriaanse M, Mutithu D, Aremu O, Stek C, du Bruyn E, Van Der Mescht MA, de Beer Z, de Villiers TR, Bodenstein A, van den Berg G, Mendes A, Strydom A, Venter M, Giandhari J, Naidoo Y, Pillay S, Tegally H, Grifoni A, Weiskopf D, Sette A, Wilkinson RJ, de Oliveira T, Bekker LG, Gray G, Ueckermann V, Rossouw T, Boswell MT, Bihman J, Moore PL, Sigal A, Ntusi NAB, Burgers WA, Riou C

Journal: Nature, 2022. DOI: doi: 10.1038/s41586-022-04460-3


The SARS-CoV-2 Omicron variant has multiple Spike (S) protein mutations that contribute to escape from antibody neutralization and reduce vaccine protection from infection. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. We assessed the ability of T cells to react with Omicron spike in participants who were vaccinated with Ad26.CoV2.S, BNT162b2, or unvaccinated convalescent COVID-19 patients (n=70). We found that 70-80% of the CD4+ and CD8+ T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar to Beta and Delta variants, despite Omicron harboring considerably more mutations. In Omicron-infected hospitalized patients (n=19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n=49). Thus, despite Omicron's extensive mutations and reduced susceptibility to neutralizing antibodies, the majority of T cell responses, induced by vaccination or infection, cross-recognize the variant. It remains to be determined whether well-preserved T cell immunity to Omicron contributes to protection from severe COVID-19, and is linked to early clinical observations from South Africa and elsewhere