Figure 9. Graphical study summary.

Antibody responses to SARS-CoV-2 and endemic CoV spike proteins were measured in diverse cohorts. While antibodies to SARS-CoV-2 were induced across all isotypes, only IgA and IgG responses to endemic CoV were robustly boosted, and only among naturally infected but not vaccinated individuals. These recalled, cross-reactive responses to endemic CoV primarily recognized the better-conserved S2 domain and were non-neutralizing. While other antiviral activities of broadly cross-reactive S2-specifc antibodies are not known, the differing antigenicity of natural infection and vaccination with stabilized prefusion spike has potential implications for the breadth and level of protection afforded by each.