Cross-reactive coronavirus antibodies with diverse epitope specificities and Fc effector functions

Andrea R. Shiakolas, Kevin J. Kramer, Daniel Wrapp, Simone I. Richardson, Alexandra Schäfer, Steven Wall, Nianshuang Wang, Katarzyna Janowska, Kelsey A. Pilewski, Rohit Venkat, Robert Parks, Nelia P. Manamela, Nagarajan Raju, Emilee Friedman Fechter, Clinton M. Holt, Naveenchandra Suryadevara, Rita E. Chen, David R. Martinez, Rachel S. Nargi, Rachel E. SuttonJulie E. Ledgerwood, Barney S. Graham, Michael S. Diamond, Barton F. Haynes, Priyamvada Acharya, Robert H. Carnahan, James E. Crowe, Ralph S. Baric, Lynn Morris, Jason S. McLellan, Ivelin S. Georgiev

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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.

Original languageEnglish
Article number100313
JournalCell Reports Medicine
Volume2
Issue number6
DOIs
StatePublished - Jun 15 2021

Keywords

  • COVID-19
  • Fc effector function
  • LIBRA-seq
  • SARS-CoV-2
  • antibody discovery
  • cross-reactivity
  • single-cell sequencing

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