Endemic penetrance of SARS-CoV-2 has impacted marginally on immunity to spike protein of human coronaviruses.

SARS-CoV-2 has emerged as the 5th endemic coronavirus and immunological cross protection between coronaviruses will influence their infectivity and clinical impact. We determined adaptive immunity against the spike protein of each human coronavirus during the course of the COVID-19 pandemic. A characteristic pattern of HCoV immunodominance, dominated by OC43 and 229E, was apparent prior to SARS-CoV-2 and was largely unaffected by SARS-CoV-2 infection, which itself elicited moderate antibody titre. Vaccination or hybrid immunity elicited supraphysiological levels of coronavirus-specific antibodies, only a proportion of which was cross-reactive with SARS-CoV-2 spike indicating substantial backboosting of HCoV-specific responses. SARS-CoV-2 vaccination focused antibody responses against the S1 domain of SARS-CoV-2 spike whilst T cell responses recognised peptides equivalently across S1 and S2. Coronavirus-specific T cells exhibited strong production of IFN-γ, IL-2 and CXCL8. In summary, the entry of SARS-CoV-2 into its ecological niche has impacted marginally on relative immunity against other human coronaviruses although vaccination provides a modest antibody increment which is unlikely to be maintained. Further, although SARS-CoV-2 vaccination elicits spike-specific adaptive immune responses that are focused against the S1 domain, thereby favouring neutralising antibodies, the natural history of HCoV immunity indicates that adaptive responses may transition towards S2 recognition across the life course.