Panpan Zhou, M. Yuan, G. Song, N. Beutler, N. Shaabani, Deli Huang, Wan-ting He, Xueyong Zhu, Sean Callaghan, Peter Yong, F. Anzanello, Linghang Peng, James Ricketts, M. Parren, Elijah Garcia, Stephen A. Rawlings, Davey M. Smith, D. Nemazee, J. Teijaro, T. Rogers, I. Wilson, D. Burton, R. Andrabi
bioRxiv : the preprint server for biology, 2021
We recently described CC40.8 bnAb from a COVID-19 donor that exhibits broad reactivity with human β-CoVs. Here, we show that CC40.8 targets the conserved S2 stem-helix region of the coronavirus spike fusion machinery. We determined a crystal structure of CC40.8 Fab with a SARS-CoV-2 S2 stem-peptide at 1.6 Å resolution and found that the peptide adopts a mainly helical structure. Conserved residues in β-CoVs interact with the antibody, thereby providing a molecular basis for its broad reactivity. CC40.8 exhibits in vivo protective efficacy against SARS-CoV-2 challenge in a hamster model with reduction in weight loss and lung viral titers. Furthermore, we noted CC40.8-like bnAbs are relatively rare in human COVID-19 infection and therefore their elicitation may require rational vaccine strategies. Overall, our study describes a new target on CoV spikes for protective antibodies that may facilitate the development of pan-β-CoV vaccines. SUMMARY A human mAb isolated from a COVID-19 donor defines a protective cross-neutralizing epitope promising for pan-β-CoV vaccine strategies
Cited by 7 publications.
Field of study: Biology