SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron
• T cells of vaccinees recognize SARS-CoV-2 variants including Omicron.
• RBD memory B cells recognition of Omicron is reduced.
• A median of 11 CD4 and 10 CD8 spike epitopes are recognized in vaccinees.
• Average preservation > 80% for Omicron at the epitope level.
We address whether T cell responses induced by different vaccine platforms (mRNA-1273, BNT162b2, Ad26.COV2.S, NVX-CoV2373) cross-recognize early SARS-CoV-2 variants. T cell responses to early variants were preserved across vaccine platforms. By contrast, significant overall decreases were observed for memory B cells and neutralizing antibodies. In subjects ∼6 months post-vaccination, 90% (CD4+) and 87% (CD8+) of memory T cell responses were preserved against variants on average by AIM assay, and 84% (CD4+) and 85% (CD8+) preserved against Omicron. Omicron RBD memory B cell recognition was substantially reduced to 42% compared to other variants. T cell epitope repertoire analysis revealed a median of 11 and 10 spike epitopes recognized by CD4+ and CD8+ T cells, with average preservation > 80% for Omicron. Functional preservation of the majority of T cell responses may play an important role as second-level defenses against diverse variants.