Vaccine-elicited murine antibody WS6 neutralizes diverse beta-coronaviruses by recognizing a helical stem supersite of vulnerability
Immunization with the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) generates a variety of antibodies, but it remains uncertain whether any of these antibodies can broadly neutralize other beta-coronaviruses. In this study, we describe the antibody WS6, identified from a mouse immunized with mRNA encoding the SARS-CoV-2 spike. WS6 was shown to bind to a range of beta-coronavirus spikes and neutralize SARS-CoV-2 variants, SARS-CoV, and related sarbecoviruses. Epitope mapping revealed that WS6 targets a conserved region within the S2 subunit, shared among SARS-CoV-2, Middle East respiratory syndrome (MERS)-CoV, and hCoV-OC43. The crystal structure of WS6 at 2 Å resolution showed that its binding focuses on a conserved helix in the S2 subunit, which is hidden in both pre- and post-fusion spike conformations. Structural and neutralization data suggested that WS6 neutralizes the virus by inhibiting the fusion process after viral attachment. A comparison of WS6 with other recently discovered broadly neutralizing antibodies identified a stem-helical “supersite,” centered on hydrophobic residues Phe1148, Leu1152, Tyr1155, and Phe1156, as a promising target for future vaccine development.