Omicron BA.2 breakthrough infection elicits CD8 <sup>+</sup> T cell responses recognizing the spike of later Omicron subvariants
Sang-Hoon Kim, Jihye Kim, Sungmin Jung, Ji Yun Noh, Jin Nam Kim, Heedo Park, Young Goo Song, Kyong Ran Peck, Su‐Hyung Park, Man‐Seong Park, Jae‐Hoon Ko, Joon Young Song, Jun Yong Choi, Min Kyung Jung, Eui‐Cheol Shin
Abstract
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.