Cross-reactive coronavirus antibodies with diverse epitope specificities and extra-neutralization functions
Andrea R. Shiakolas,
Kevin J. Kramer,
Simone I. Richardson,
Kelsey A. Pilewski,
Nelia P. Manamela,
Emilee Friedman Fechter,
Clinton M. Holt,
Rita E. Chen,
David R. Martinez,
Rachel S Nargi,
Rachel E Sutton,
Julie E. Ledgerwood,
Michael S. Diamond,
Barton F Haynes,
Robert H. Carnahan,
James E. Crowe,
Jason S McLellan,
Ivelin S. Georgiev
Posted 20 Dec 2020
bioRxiv DOI: 10.1101/2020.12.20.414748
Posted 20 Dec 2020
The continual emergence of novel coronavirus (CoV) strains, like SARS-CoV-2, highlights the critical need for broadly reactive therapeutics and vaccines against this family of viruses. Coronavirus spike (S) proteins share common structural motifs that could be vulnerable to cross-reactive antibody responses. To study this phenomenon in human coronavirus infection, we applied a high-throughput sequencing method called LIBRA-seq (Linking B cell receptor to antigen specificity through sequencing) to a SARS-CoV-1 convalescent donor sample. We identified and characterized a panel of six monoclonal antibodies that cross-reacted with S proteins from the highly pathogenic SARS-CoV-1 and SARS-CoV-2 and demonstrated a spectrum of reactivity against other coronaviruses. Epitope mapping revealed that these antibodies recognized multiple epitopes on SARS-CoV-2 S, including the receptor binding domain (RBD), N-terminal domain (NTD), and S2 subunit. Functional characterization demonstrated that the antibodies mediated a variety of Fc effector functions in vitro and mitigated pathological burden in vivo. The identification of cross-reactive epitopes recognized by functional antibodies expands the repertoire of targets for pan-coronavirus vaccine design strategies that may be useful for preventing potential future coronavirus outbreaks.
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