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Front Immunol . The XBB.1.5 mRNA booster vaccine does not significantly increase the percentage of XBB.1.5 mono-reactive T cells

tetano

Editor, Senior Moderator
Front Immunol


. 2025 Mar 12:16:1513175.
doi: 10.3389/fimmu.2025.1513175. eCollection 2025. The XBB.1.5 mRNA booster vaccine does not significantly increase the percentage of XBB.1.5 mono-reactive T cells

Joel Sop[SUP] 1 [/SUP], Alicia Mercado[SUP] 1 [/SUP], Alexis Figueroa[SUP] 1 [/SUP], Tyler P Beckey[SUP] 1 [/SUP], Caroline C Traut[SUP] 1 [/SUP], Li Zhang[SUP] 2 3 [/SUP], Kellie N Smith[SUP] #[/SUP][SUP] 2 3 [/SUP], Joel N Blankson[SUP] #[/SUP][SUP] 1 [/SUP]



Affiliations
Abstract

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 cell-mediated 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 mono-reactive T cell responses by variant-specific booster vaccines.

Keywords: BA.2.86; SARS-CoV-2; T cell receptor; XBB.1.5; bivalent vaccine.

 
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