Aging and viral evolution impair dominant pan-coronavirus-reactive immunity against SARS-CoV-2
LOYAL L. 1,2, JÜRCHOTT K. 1,2, MEYER-ARNDT L. 1,2, HENZE L. 1,2, KRUSE B. 1,2, DINGELDEY M. 1,2, MANGOLD M. 1,2, BRAUN J. 1,2, KERN F. 3, THIEL A. 1,2
1 Berlin Institute of Health (BIH) at Charité – Universitätsmedizin Berlin, Immunomics - Regenerative Immunology and Aging, Berlin, Germany; 2 Si-M / “Der Simulierte Mensch” a science framework of Technische Universität Berlin and Charité - Universitätsmedizin Berlin, Berlin, Germany; 3 Department of Clinical and Experimental Medicine, Brighton and Sussex Medical School, Brighton, United Kingdom
Immune evasion by escape mutations subverts immunity against SARS-CoV-2. A role of pan-coronavirus immunity for more durable protection also against potentially arising future coronavirus outbreaks is being discussed but has remained understudied. We here investigated the effects of age, mutations, and homo-/heterologous vaccination regimens on pan-coronavirus-specific cellular and humoral immunity after SARS-CoV-2 infection and vaccination in detail. In the older, quantitatively, and qualitatively reduced pan-coronavirus-reactive CD4+ T cell responses with narrow TCR repertoires and lost public clones 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.