Aging and viral evolution impair immunity against dominant pan-coronavirus-reactive T cell epitope
Author:
Loyal LucieORCID, Jürchott Karsten, Reimer Ulf, Meyer-Arndt Lil, Henze Larissa, Mages Norbert, Kostrzanowski Jak, Reus Bernhard, Mangold Maike, Kruse Beate, Dingeldey Manuela, Sawitzki Birgit, Michel JanineORCID, Grossegesse Marica, Schnatbaum Karsten, Wenschuh Holger, Nitsche Andreas, Lachmann Nils, Timmermann Bernd, Giesecke-Thiel Claudia, Braun Julian, Kern Florian, Thiel Andreas
Abstract
AbstractImmune 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
Publisher
Cold Spring Harbor Laboratory
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