Publication date: Jan 19, 2024
Here, we examine peripheral blood memory T cell responses against the SARS-CoV-2 BA. 4/BA. 5 variant spike among vaccinated individuals with or without Omicron breakthrough infections. We provide evidence supporting a lack of original antigenic sin in CD8 T cell responses targeting the spike. We show that BNT162b2-induced memory T cells respond to the BA. 4/BA. 5 spike. Among individuals with BA. 1/BA. 2 breakthrough infections, IFN-γ-producing CD8 T cell responses against the BA. 4/BA. 5 spike increased. In a subgroup with BA. 2 breakthrough infections, IFN-γ-producing CD8 T cell responses against the BA. 2-mutated spike region increased and correlated directly with responses against the BA. 4/BA. 5 spike, indicating that BA. 2 spike-specific CD8 T cells elicited by BA. 2 breakthrough infection cross-react with the BA. 4/BA. 5 spike. We identified CD8 T cell epitope peptides that are present in the spike of BA. 2 and BA. 4/BA. 5 but not the original spike. These peptides are fully conserved in the spike of now-dominant XBB lineages. Our study shows that breakthrough infection by early Omicron subvariants elicits CD8 T cell responses that recognize epitopes within the spike of newly emerging subvariants.