T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all individuals
Vivek Naranbhai, Anusha Nathan, Clarety Kaseke, Cristhian Berrios, Ashok Khatri, Shawn Choi, Matthew A. Getz, Rhoda Tano-Menka, Onosereme Ofoman, Alton C. Gayton, Fernando Senjobe, Zezhou Zhao, Kerri St. Denis, Evan C. Lam, Mary Carrington, Wilfredo F. García-Beltrán, Alejandro B. Balazs, Bruce D. Walker, A. John Iafrate, Gaurav D. Gaiha
Abstract
The SARS-CoV-2 Omicron variant (B.1.1.529) contains mutations that mediate escape from antibody responses, although the extent to which these substitutions in spike and non-spike proteins affect T cell recognition is unknown. In this study, we show that T cell responses in individuals with prior infection, vaccination, both prior infection and vaccination, and boosted vaccination are largely preserved to Omicron spike and non-spike proteins. However, we also identify a subset of individuals (∼21%) with a >50% reduction in T cell reactivity to the Omicron spike. Evaluation of functional CD4+ and CD8+ memory T cell responses confirmed these findings and revealed that reduced recognition to Omicron spike is primarily observed within the CD8+ T cell compartment potentially due to escape from HLA binding. Booster vaccination enhanced T cell responses to Omicron spike. In contrast to neutralizing immunity, these findings suggest preservation of T cell responses to the Omicron variant, although with reduced reactivity in some individuals.