The impact of ageing on SARS-CoV-2 and human coronavirus reactive antibodies after COVID-19 vaccination or infection

Abstract

The endemic human coronavirus (HCoV) circulates worldwide yet remain understudied and unmitigated. The observation of elevated levels of HCoV reactive antibodies in COVID-19 patients highlights the urgent necessity of better understanding of HCoV specific immunity. Here, we characterized in-depth the de novo SARS-CoV-2 specific antibody responses and the boosting of HCoV-reactive antibodies after SARS-CoV-2 vaccination and infection in individuals up to 98 years old. The first two vaccine doses elicited potent SARS-CoV-2 spike binding antibodies in individuals up to 80 years old. The third dose largely boosted the previously low S2 domain binding and neutralizing antibodies in elderly 80–90 years old, but less so in those above 90 years. The endemic betacoronavirus (HKU1 and OC43) reactive antibodies were boosted in all vaccinees, although to a lesser extent in those above 80 years old. COVID-19 patients had potent elevation of alpha- and betacoronavirus (229E, NL63, HKU1 and OC43) reactive antibodies. In both patients and vaccinees, S2 domain specific antibody increases correlated with SARS-CoV-2 neutralizing and HCoV-reactive antibody responses in all ages, indicating S2 domain as a candidate for future universal coronavirus vaccine design.