Aging and viral evolution impair immunity against dominant pan-coronavirus-reactive T cell epitope

Loyal, L.; Juerchott, K.; Reimer, U.; Meyer-Arndt, L.; Henze, L.; Mages, N.; Kostrzanowski, J.; Reus, B.; Mangold, M.; Kruse, B.; Dingeldey, M.; Sawitzki, B.; Wenschuh, H.; Michel, J.; Grossegesse, M.; Nitsche, A.; Lachmann, N.; Timmermann, B.; Giesecke, C.; Braun, J.; Kern, F.; Thiel, A.

doi:10.1101/2024.08.21.608923

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bioRxiv · 10.1101/2024.08.21.608923

Aging and viral evolution impair immunity against dominant pan-coronavirus-reactive T cell epitope

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Abstract

Immune evasion by escape mutations subverts immunity against SARS-CoV-2. A role of pan-coronavirus immunity for more durable protection is being discussed but has remained understudied. We here investigated the effects of age, mutations, and homo-/heterologous vaccination regimens on the dominant pan-coronavirus-specific cellular and humoral epitope iCope after SARS-CoV-2 infection and vaccination in detail. In the older, quantitatively, and qualitatively reduced iCope-reactive CD4+ T cell responses with narrow TCR repertoires could not be enhanced by vaccination and were further compromised by emerging spike mutations. In contrast pan-coronavirus-reactive humoral immunity was affected only by mutations and not by age. Our results reveal a distinct deficiency of the dichotomous layer of pan-coronavirus immunity in the older, critical for long-term protection against SARS-CoV-2 variants. One-Sentence SummaryAging and viral evolution impair dominant pan-coronavirus immunity, a hallmark of efficient and broad immune competence against SARS-CoV-2

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Loyal, L., Juerchott, K., Reimer, U., Meyer-Arndt, L., Henze, L., Mages, N., Kostrzanowski, J., Reus, B., Mangold, M., Kruse, B., Dingeldey, M., Sawitzki, B., Wenschuh, H., Michel, J., Grossegesse, M., Nitsche, A., Lachmann, N., Timmermann, B., Giesecke, C., Braun, J., Kern, F., Thiel, A.. 2024-08-21. Aging and viral evolution impair immunity against dominant pan-coronavirus-reactive T cell epitope. https://doi.org/10.1101/2024.08.21.608923

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