Andrea R. Shiakolas, Kevin J. Kramer, D. Wrapp, Simone I. Richardson, A. Schäfer, S. Wall, N. Wang, K. Janowska, Kelsey A. Pilewski, R. Venkat, R. Parks, Nelia P. Manamela, Nagarajan Raju, Emilee Friedman Fechter, Clinton M. Holt, Naveenchandra Suryadevara, Rita E. Chen, D. R. Martinez, Rachel S. Nargi, Rachel E. Sutton, J. Ledgerwood, B. Graham, M. Diamond, B. Haynes, P. Acharya, R. Carnahan, J. Crowe, R. Baric, L. Morris, J. McLellan, I. Georgiev
bioRxiv : the preprint server for biology, 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.
Cited by 4 publications.
Field of study: Medicine