Structural mapping of antibody landscapes to human betacoronavirus spike proteins

Bangaru, Sandhya; Antanasijevic, Aleksandar; Kose, Nurgun; Sewall, Leigh M.; Jackson, Abigail M.; Suryadevara, Naveenchandra; Zhan, Xiaoyan; Torres, Jonathan L.; Copps, Jeffrey; Torrents de la Peña, Alba; Crowe, James E.; Ward, Andrew B.

Preexisting immunity against seasonal coronaviruses (CoV) represents an important variable in predicting antibody responses and disease severity to Severe Acute Respiratory Syndrome CoV-2 (SARS-2) infections. We used electron microscopy based polyclonal epitope mapping (EMPEM) to characterize the antibody specificities against β-CoV spike proteins in sera from healthy donors (HDs) or SARS-2 convalescent donors (CDs). We observed that most HDs possessed antibodies specific to seasonal human CoVs (HCoVs) OC43 and HKU1 spike proteins while the CDs showed reactivity across all human β-CoVs. Detailed molecular mapping of spike-antibody complexes revealed epitopes that were differentially targeted by antibodies in preexisting and convalescent serum. Our studies provide an antigenic landscape to β-HCoV spikes in the general population serving as a basis for cross-reactive epitope analyses in SARS-2 -infected individuals. One-Sentence summary We present the epitope mapping of polyclonal antibodies against beta-coronavirus spike proteins in human sera.