Humoral immunity to endemic coronaviruses in older adults increases post-COVID-19 vaccination and in correlation with their anti-SARS-CoV-2 responses

Advanced age is an established risk factor for SARS-CoV-2 infection and severe disease. Older adults, having experienced recurrent infections with human endemic coronaviruses (HCoVs) throughout life, may have developed humoral immune responses that impact IgG targeting of both severe acute respiratory syndrome coronavirus (SARS-CoV) -2 and HCoVs. We profiled IgG responses in community-dwelling adults aged 50-87 years from the "PRospEctiVe EvaluatioN of immunity after COVID-19 vaccines" (PREVENT-COVID) prospective cohort study. Dried blood spot sampling occurred at baseline, prior to detected SARS-CoV-2 antigen exposure, and throughout the recommended vaccination schedule in Canada for SARS-CoV-2 seronegative and seropositive individuals. We define an HCoV-OC43-IgG high and HCoV-NL63-low baseline antibody landscape, which was unaffected by age or sex. Following COVID-19 vaccination, we observed increased anti HCoV-OC43 and HCoV-HKU1 IgG antibody titers, with substantial waning between doses. IgG specific to beta-coronaviruses and SARS-CoV-2 spike antigens positively correlated, strengthening with subsequent doses. In contrast, SARS-CoV-2 anti-nucleocapsid (N) antibodies associated most closely with HCoV-NL63 IgG levels. These findings suggest that HCoV-specific humoral immunity induced by COVID-19 vaccination or disease may impact susceptibility to future coronavirus infection. ACE2-binding assays revealed that individuals with greater HCoV-OC43- and HCoV-HKU1-specific IgG levels had the highest percent neutralization of the wildtype virus and SARS-CoV-2 variants. Together, our study highlights potential effects of COVID-19 vaccination on humoral immunity towards related coronaviruses.