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

Cell Rep Med. 2021 Jun 15;2(6):100313. doi: 10.1016/j.xcrm.2021.100313. Epub 2021 May 21.


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.

Keywords: COVID-19; Fc effector function; LIBRA-seq; SARS-CoV-2; antibody discovery; cross-reactivity; single-cell sequencing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antigen-Antibody Reactions
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism
  • COVID-19 / pathology
  • COVID-19 / virology
  • Cell Line
  • Cross Reactions / immunology
  • Epitope Mapping
  • Epitopes / immunology*
  • Female
  • Humans
  • Immunoglobulin Fc Fragments / immunology
  • Immunoglobulin Fc Fragments / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Phagocytosis
  • Protein Subunits / immunology
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / metabolism
  • Severe acute respiratory syndrome-related coronavirus / immunology
  • Severe acute respiratory syndrome-related coronavirus / metabolism
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology*
  • Spike Glycoprotein, Coronavirus / metabolism


  • Antibodies, Monoclonal
  • Epitopes
  • Immunoglobulin Fc Fragments
  • Protein Subunits
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2