Antigenic mapping reveals sites of vulnerability on α-HCoV spike protein

Understanding the antigenic signatures of all human coronaviruses (HCoVs) Spike (S) proteins is imperative for pan-HCoV epitopes identification and broadly effective vaccine development. To depict the currently elusive antigenic signatures of alpha-HCoVs S proteins, we isolated a panel of antibodies against the HCoV-229E S protein and characterized their epitopes and neutralizing potential. We found that the N-terminal domain of HCoV-229E S protein is antigenically dominant wherein an antigenic supersite is present and appears conserved in HCoV-NL63, which holds potential to serve as a pan-alpha-HCoVs epitope. In the receptor binding domain, a neutralizing epitope is captured in the end distal to the receptor binding site, reminiscent of the locations of the SARS-CoV-2 RBD cryptic epitopes. We also identified a neutralizing antibody that recognizes the connector domain, thus representing the first S2-directed neutralizing antibody against alpha-HCoVs. The unraveled HCoVs S proteins antigenic similarities and variances among genera highlight the challenges faced by pan-HCoV vaccine design while supporting the feasibility of broadly effective vaccine development against a subset of HCoVs. The antigenic landscape of alpha-HCoVs S proteins is revealed, highlighting the challenges faced by pan-HCoV vaccine design but also revealing opportunities for development of broadly effective vaccines against a subset of HCoVs.

Automated summary

Understanding the antigenic signatures of human coronaviruses is crucial for vaccine development. Researchers have identified antigenic sites in the S proteins of HCoV-229E and HCoV-NL63, which may serve as targets for pan-alpha-HCoVs vaccines. They have also discovered a neutralizing antibody that targets the connector domain, representing the first S2-directed neutralizing antibody against alpha-HCoVs. These findings provide insights into the antigenic landscape of alpha-HCoVs S proteins and the challenges and opportunities in pan-HCoV vaccine design.