Cross reactive T cells hold up against Omicron

After a flurry of articles describing antibody evasion by Omicron, several reports now detail cellular immune responses against the highly mutated SARS-CoV-2 variant. Investigating CD4⁺ and CD8⁺ T cells in vaccinated and convalescent individuals, these studies show a high degree of preservation of T cell epitopes between the ancestral strain and Omicron. However, the degree of cross-reactivity varied among individuals, likely as a consequence of genetic aspects of antigen presentation. Gao et al. report a significantly lower magnitude of responses to the Omicron spike protein in T cells from convalescent compared to BNT162b2 vaccinated individuals, indicating that ‘boosting’ may benefit those with ‘natural immunity’. Keeton et al. also investigated patients hospitalized with Omicron and found a similar magnitude of T cell responses as previously observed in patients infected with other variants. A comprehensive analysis of T cell responses against variants from Alpha to Omicron, at different time points after vaccination (with BNT162b2, mRNA-1273, Ad26.CoV2.S or NVX-CoV2373), was presented by Tarke et al. It shows that 84% of CD4⁺ and 85% of CD8⁺ memory T cell responses to the Omicron spike protein are preserved, compared to an average of 90% and 87% respectively for the other variants. This contrasts sharply with a marked reduction of memory B cell recognition of Omicron spike. Overall, these observations could explain why vaccines or previous infection still provide robust protection against severe disease with Omicron, even when levels of neutralizing antibodies are insufficient to prevent infection, and indicate that viral evolution is not driven by T cell escape.