Accelerated memory T cell decline and tolerogenic recall responses to SARS-CoV-2 vaccination in diabetes

Jones, E. M.; Sourij, C.; Stradner, M.; Schlenke, P.; Sereban, N.; Moser, O.; Quinlan, R.; Short, C.-E.; Harris, B. H. L.; Fertleman, M.; Taylor, G. P.; Oliver, N.; Sourij, H.; Dominguez-Villar, M.

doi:10.1101/2025.02.08.637262

bioRxiv · 10.1101/2025.02.08.637262

Accelerated memory T cell decline and tolerogenic recall responses to SARS-CoV-2 vaccination in diabetes

Jones, E. M.·Sourij, C.·Stradner, M.·Schlenke, P.·Sereban, N.·Moser, O.·Quinlan, R.·Short, C.-E.·Harris, B. H. L.·Fertleman, M.·Taylor, G. P.·Oliver, N.·Sourij, H.·Dominguez-Villar, M.

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Abstract

Type 1 and type 2 diabetes are associated with increased severity and mortality from respiratory virus infections, including SARS-CoV-2. Vaccination in the general population significantly reduces the risk of severe respiratory viral infection and triggers a strong, polyfunctional and lasting T cell response in healthy individuals. However, vaccine effectiveness in people with diabetes is unclear. Here we studied the magnitude and functional characteristics of vaccine-specific CD4+ and CD8+ T cell responses to the full vaccination protocol, and the recall response after a third booster dose of SARS-CoV-2 vaccine in people with type 1 and type 2 diabetes, and compared them to those of people without diabetes. We found defects in both CD4+ and CD8+ T cell memory maintenance and the functionality of the vaccine specific T cells in people with diabetes compared to people without. In those individuals with diabetes that harbored detectable vaccine-specific T cells, they displayed an unfocused, tolerogenic phenotype characterized by increased expression of IL-13 and IL-10 in T1D and T2D compared to people without diabetes. These results have implications for vaccination strategies for people with diabetes.

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Jones, E. M., Sourij, C., Stradner, M., Schlenke, P., Sereban, N., Moser, O., Quinlan, R., Short, C.-E., Harris, B. H. L., Fertleman, M., Taylor, G. P., Oliver, N., Sourij, H., Dominguez-Villar, M.. 2025-02-11. Accelerated memory T cell decline and tolerogenic recall responses to SARS-CoV-2 vaccination in diabetes. https://doi.org/10.1101/2025.02.08.637262

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