T cell responses to COVID-19 bivalent booster vaccine 2422

Abstract Description The impact of the emerging SARS-CoV-2 variants during the COVID-19 pandemic spurred efforts to update the original COVID-19 vaccines to include the new mutations. During 2022-2023, COVID-19 vaccination guidelines recommended boosting with an updated bivalent mRNA formula, combining the original Spike and the Omicron BA.4/BA.5 Spike sequences. Several studies have addressed the antibody responses following the bivalent booster, but its effect on T cells remains uncertain. T cells constitute a pivotal component of the COVID-19 response, being associated with long lasting immunity and reduced hospitalization. In this study, we analyzed the Spike-specific T cell response following the bivalent booster vaccination (by either Pfizer/BioNTech or Moderna) in humans. Peripheral blood mononuclear cells (PBMCs) were obtained 32 (±16) days post vaccination and stimulated with Spike peptide mega pools (MPs) to measure their vaccine-induced reactivity. We performed an in-depth profiling of T cells, assessing activation markers, cytokine production, and the impact of Spike variants. Overall, our results indicate that the bivalent booster induced comparable responses to Ancestral, BA.4-5 and XBB.1 MPs. This supports the evidence that T cells responses are not significantly impacted by mutations in the Spike of the new variants. We also show how the booster proved to be beneficial for individuals with poor or declining T cell responses, increasing the frequency of specific T cells in blood. Funding Sources This project has been funded in whole or in part with Federal funds from the US National Cancer Institute grant U01CA260541 (D.W.) and from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. 75N93021C00016 (A.G.). Topic Categories Vaccines and Immunotherapy (VAC)