The XBB.1.5 mRNA booster vaccine does not significantly increase the percentage of XBB.1.5 monoreactive T cells

Joel Sop ¹ Alicia Mercado ¹ Alexis Figueroa ¹ Tyler Beckey ¹ Caroline Traut ¹ Li Zhang ¹ Kellie N Smith ¹ Joel Blankson ^1,2*

• ¹ Johns Hopkins Medicine, Johns Hopkins University, Baltimore, Maryland, United States
• ² Johns Hopkins University, Baltimore, United States

Recent efforts in vaccine development have targeted spike proteins from evolving SARS-CoV-2 variants.In this study, we analyzed T cell responses to the XBB.1.5 and BA.2.86 subvariants in individuals who previously received bivalent vaccines containing mRNA for ancestral and BA.5 spike proteins. T cellmediated cytokine responses to spike proteins from both variants were largely preserved. To determine the mechanism of this preserved recognition, we utilized the functional expansion of specific T cells (FEST) assay to distinguish between the presence of T cells that cross-recognized ancestral and variant epitopes versus distinct populations of T cells that were mono-reactive for ancestral or variant epitopes.We found the majority of spike-specific T cells cross-recognized the ancestral spike and the XBB.1.5 and BA.2.86 subvariants, with less than 10% of T cells being mono-reactive for either variant. Interestingly, immunization with the XBB.1.5 monovalent booster vaccine did not significantly increase the percentage of XBB.1.5 mono-reactive T cells. Our results suggest a potential limitation in the induction of monoreactive T cell responses by variant-specific booster vaccines.