Broad sarbecovirus neutralizing antibodies define a key site of vulnerability on the SARS-CoV-2 spike protein

Walker, L. M.; Wec, A. Z.; Wrap, D.; Herbert, A. S.; Maurer, D. P.; Haslwanter, D.; Sakharkar, M.; Jangra, R. K.; Dieterle, M. E.; Lilov, A.; Huang, D.; Tse, L. V.; Johnson, N. V.; Hsieh, C.-L.; Wang, N.; Nett, J. H.; Champney, E.; Burnina, I.; Brown, M.; Lin, S.; Sinclair, M.; Johnson, C.; Pudi, S.; Bortz, R.; Wirchnianski, A. S.; Laudermilch, E.; Florez, C.; Fels, J. M.; O'Brien, C. M.; Graham, B. S.; Nemazee, D.; Burton, D. R.; Baric, R. S.; Voss, J. E.; Chandran, K.; Dye, J. M.; McLellan, J. S.

doi:10.1101/2020.05.15.096511

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bioRxiv · 10.1101/2020.05.15.096511

Broad sarbecovirus neutralizing antibodies define a key site of vulnerability on the SARS-CoV-2 spike protein

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Abstract

Broadly protective vaccines against known and pre-emergent coronaviruses are urgently needed. Critical to their development is a deeper understanding of cross-neutralizing antibody responses induced by natural human coronavirus (HCoV) infections. Here, we mined the memory B cell repertoire of a convalescent SARS donor and identified 200 SARS-CoV-2 binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of pre-existing memory B cells (MBCs) elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a new target for the rational design of pan-sarbecovirus vaccines.

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Walker, L. M., Wec, A. Z., Wrap, D., Herbert, A. S., Maurer, D. P., Haslwanter, D., Sakharkar, M., Jangra, R. K., Dieterle, M. E., Lilov, A., Huang, D., Tse, L. V., Johnson, N. V., Hsieh, C.-L., Wang, N., Nett, J. H., Champney, E., Burnina, I., Brown, M., Lin, S., Sinclair, M., Johnson, C., Pudi, S., Bortz, R., Wirchnianski, A. S., Laudermilch, E., Florez, C., Fels, J. M., O'Brien, C. M., Graham, B. S., Nemazee, D., Burton, D. R., Baric, R. S., Voss, J. E., Chandran, K., Dye, J. M., McLellan, J. S.. 2020-05-15. Broad sarbecovirus neutralizing antibodies define a key site of vulnerability on the SARS-CoV-2 spike protein. https://doi.org/10.1101/2020.05.15.096511

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