Cross-reactive coronavirus antibodies with diverse epitope specificities and Fc effector functions.
Journal Article (Journal Article)
The continual emergence of novel coronaviruses (CoV), such as severe acute respiratory syndrome-(SARS)-CoV-2, highlights the critical need for broadly reactive therapeutics and vaccines against this family of viruses. From a recovered SARS-CoV donor sample, we identify and characterize a panel of six monoclonal antibodies that cross-react with CoV spike (S) proteins from the highly pathogenic SARS-CoV and SARS-CoV-2, and demonstrate a spectrum of reactivity against other CoVs. Epitope mapping reveals that these antibodies recognize multiple epitopes on SARS-CoV-2 S, including the receptor-binding domain, the N-terminal domain, and the S2 subunit. Functional characterization demonstrates that the antibodies mediate phagocytosis-and in some cases trogocytosis-but not neutralization in vitro. When tested in vivo in murine models, two of the antibodies demonstrate a reduction in hemorrhagic pathology in the lungs. The identification of cross-reactive epitopes recognized by functional antibodies expands the repertoire of targets for pan-coronavirus vaccine design strategies.
- Shiakolas, AR; Kramer, KJ; Wrapp, D; Richardson, SI; Schäfer, A; Wall, S; Wang, N; Janowska, K; Pilewski, KA; Venkat, R; Parks, R; Manamela, NP; Raju, N; Fechter, EF; Holt, CM; Suryadevara, N; Chen, RE; Martinez, DR; Nargi, RS; Sutton, RE; Ledgerwood, JE; Graham, BS; Diamond, MS; Haynes, BF; Acharya, P; Carnahan, RH; Crowe, JE; Baric, RS; Morris, L; McLellan, JS; Georgiev, IS
- June 15, 2021
Volume / Issue
- 2 / 6
Start / End Page
- 100313 -
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)
- United States