Aging and viral evolution impair pan-coronavirus immunity 2342

Abstract Description Repeated vaccinations and infections have led to diverse states of hybrid immunity against SARS-CoV-2 in the global population. Yet, age and comorbidities can compromise protection against severe disease, and antibody-mediated immunity in particular is undercut by viral immune escape mutations and aging. Whether and to which extent durable pan-coronavirus T cell responses compensate for this reduced humoral immunity is not fully understood. In the older, the quantitatively and qualitatively impaired CD4+ T cell responses against the immunodominant T cell epitope iCope (S816-830) could not be enhanced by vaccination and were further compromised by emerging spike mutations. In contrast, iCope-specific humoral response was only affected by mutations and not by age. However, sets of multiple pan-coronavirus epitopes compensated for the single epitope shortcoming in cellular immunity with comparable antigen-specific T cell frequencies and functional TCR avidities across all age groups, and only with reduced polyfunctionality in the very old. Altogether, our results reveal diverse deficiencies in the dichotomous layer of pan-coronavirus immunity, especially in the elderly, critical for long-term protection against SARS-CoV-2 variants and potential future spillovers. Funding Sources Funded by Federal Ministry of Health (Germany), Charité Corona Cross 2.0 and Charité Corona Protect. Topic Categories Viral Immunology (VIR)