A public vaccine-induced human antibody protects against SARS-CoV-2 and emerging variants

Schmitz, Aaron J.; Turner, Jackson S.; Liu, Zhuoming; Aziati, Ishmael D.; Chen, Rita E.; Joshi, Astha; Bricker, Traci L.; Darling, Tamarand L.; Adelsberg, Daniel C.; Alsoussi, Wafaa B.; Case, James Brett; Lei, Tingting; Thapa, Mahima; Amanat, Fatima; O’Halloran, Jane A.; Shi, Pei-Yong; Presti, Rachel M.; Krammer, Florian; Bajic, Goran; Whelan, Sean P.J.; Diamond, Michael S.; Boon, Adrianus C. M.; Ellebedy, Ali H.

The emergence of antigenically distinct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility is a public health threat. Some of these variants show substantial resistance to neutralization by SARS-CoV-2 infection- or vaccination-induced antibodies, which principally target the receptor binding domain (RBD) on the virus spike glycoprotein. Here, we describe 2C08, a SARS-CoV-2 mRNA vaccine-induced germinal center B cell-derived human monoclonal antibody that binds to the receptor binding motif within the RBD. 2C08 broadly neutralizes SARS-CoV-2 variants with remarkable potency and reduces lung inflammation, viral load, and morbidity in hamsters challenged with either an ancestral SARS-CoV-2 strain or a recent variant of concern. Clonal analysis identified 2C08-like public clonotypes among B cell clones responding to SARS-CoV-2 infection or vaccination in at least 20 out of 78 individuals. Thus, 2C08-like antibodies can be readily induced by SARS-CoV-2 vaccines and mitigate resistance by circulating variants of concern.