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

Abstract

The SARS-CoV-2 Omicron variant (B.1.1.529) has multiple spike protein mutations ^{1, 2} that contribute to viral escape from antibody neutralization ^{3– 6} and reduce vaccine protection from infection ^{7, 8} . 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. Here we assessed the ability of T cells to react to Omicron spike protein in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, or unvaccinated convalescent COVID-19 patients ( n = 70). Between 70% and 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 for Beta (B.1.351) and Delta (B.1.617.2) variants, despite Omicron harbouring considerably more mutations. In patients who were hospitalized with Omicron infections ( n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants ( n = 49). Thus, despite extensive mutations and reduced susceptibility to neutralizing antibodies of Omicron, 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 ^{9– 12} .

Abstract

T cell responses to spike protein from the SARS-CoV-2 Omicron variant (B.1.1.529) are broadly similar to the responses to ancestral, Beta (B.1.351) and Delta (B.1.617.2) spike protein in vaccinated, infected and unvaccinated individuals.