Endemic human coronaviruses induce distinct antibody repertoires in adults and children
Four endemic human coronaviruses (HCoVs) are commonly associated with acute respiratory infection in humans but immune responses to these 'common cold' viruses remain incompletely understood. Moreover, there is evidence emerging from independent studies which suggests that endemic HCoVs can induce broadly cross-reactive T cell responses and may thereby affect clinical outcomes of acute infections with the phylogenetically related epidemic viruses, namely MERS-CoV and SARS-CoV-2. Here we report
... -2. Here we report a comprehensive retrospective analysis of CoV-specific antibody specificities in a large number of samples from children and adults using Phage-Immunoprecipitation Sequencing (PhIP-Seq). We estimate the seroprevalence for endemic HCoVs to range from ~4% to ~27% depending on species and cohort. Most importantly, we identified a large number of novel linear B cell epitopes of HCoV proteins and demonstrate that antibody repertoires against endemic HCoVs are qualitatively different in children in comparison to the general adult population and healthy adult blood bank donors. We show that anti-HCoV IgG specificities more frequently found among children target functionally important and structurally conserved regions of the HCoV spike and nucleocapsid proteins and some antibody specificities are broadly cross-reactive with peptides of epidemic human and non-human coronavirus isolates. Our findings shed light on the humoral immune responses to natural infection with endemic HCoVs and may have important implications for understanding of the highly variable clinical outcomes of human coronavirus infections, for the development of prophylactic or therapeutic monoclonal antibodies and vaccine design.