Author:
Johnson Nicole V.,Wall Steven C.,Kramer Kevin J.,Holt Clinton M.,Periasamy Sivakumar,Richardson Simone,Suryadevara Naveenchandra,Andreano Emanuele,Paciello Ida,Pierleoni Giulio,Piccini Giulia,Huang Ying,Ge Pan,Allen James D.,Uno Naoko,Shiakolas Andrea R.,Pilewski Kelsey A.,Nargi Rachel S.,Sutton Rachel E.,Abu-Shmais Alexandria A.,Parks Robert,Haynes Barton F.,Carnahan Robert H.,Crowe James E.,Montomoli Emanuele,Rappuoli Rino,Bukreyev Alexander,Ross Ted M.,Sautto Giuseppe A.,McLellan Jason S.,Georgiev Ivelin S.
Abstract
SUMMARY/ABSTRACTThree coronaviruses have spilled over from animal reservoirs into the human population and caused deadly epidemics or pandemics. The continued emergence of coronaviruses highlights the need for pan-coronavirus interventions for effective pandemic preparedness. Here, using LIBRA-seq, we report a panel of 50 coronavirus antibodies isolated from human B cells. Of these antibodies, 54043-5 was shown to bind the S2 subunit of spike proteins from alpha-, beta-, and deltacoronaviruses. A cryo-EM structure of 54043-5 bound to the pre-fusion S2 subunit of the SARS-CoV-2 spike defined an epitope at the apex of S2 that is highly conserved among betacoronaviruses. Although non-neutralizing, 54043-5 induced Fc-dependent antiviral responses, including ADCC and ADCP. In murine SARS-CoV-2 challenge studies, protection against disease was observed after introduction of Leu234Ala, Leu235Ala, and Pro329Gly (LALA-PG) substitutions in the Fc region of 54043-5. Together, these data provide new insights into the protective mechanisms of non-neutralizing antibodies and define a broadly conserved epitope within the S2 subunit.
Publisher
Cold Spring Harbor Laboratory