Distinct antibody repertoires against endemic human coronaviruses in children and adults

Four endemic human coronaviruses (HCoVs) are commonly associated with acute respiratory infection in humans. B cell responses to these “common cold” viruses remain incompletely understood. Here we report a comprehensive analysis of CoV-specific antibody repertoires 231 children and 1168 adults using phage immunoprecipitation sequencing. Seroprevalence antibodies against HCoVs ranged between approximately 4% 27% depending on the species cohort. We identified at least 136 novel linear epitopes. Antibody were qualitatively different that anti-HCoV IgG specificities more frequently found among targeted functionally important structurally conserved regions spike, nucleocapsid, matrix proteins. Moreover, targeting highly fusion peptide region S2′ cleavage site spike protein broadly cross-reactive peptides epidemic nonhuman coronaviruses. In contrast, an acidic tandem repeat N-terminal Nsp3 subdomain HCoV-HKU1 polyprotein was predominant target adult donors. Our findings shed light dominant species-specific pan-CoV sites coronavirus infection, thereby providing insights for development prophylactic or therapeutic monoclonal vaccine design.