Isolation and comparative analysis of antibodies that broadly neutralize sarbecoviruses

Liu, L.; Iketani, S.; Guo, Y.; Casner, R.; Reddem, E.; Nair, M. S.; Yu, J.; Chan, J.; Wang, M.; Cerutti, G.; Li, Z.; Castagna, C.; Corredor, L.; Chu, H.; Yuan, S.; Poon, V.; Chan, C.; Chen, Z.; Luo, Y.; Cunningham, M.; Chavez, A.; Yin, M.; Perlin, D.; Tsuji, M.; Yuen, K.-Y.; Kwong, P.; Sheng, Z.; Huang, Y.; Shapiro, L.; Ho, D. D.

doi:10.1101/2021.12.11.472236

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bioRxiv · 10.1101/2021.12.11.472236

Isolation and comparative analysis of antibodies that broadly neutralize sarbecoviruses

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Abstract

The devastation caused by SARS-CoV-2 has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptor-binding domain (RBD)-directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses and thus its promise as an agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well conserved among sarbecoviruses, but also uncovered a new antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine. One sentence summaryA monoclonal antibody that neutralizes or binds all sarbecoviruses tested and represents a reproducible antibody class.

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Liu, L., Iketani, S., Guo, Y., Casner, R., Reddem, E., Nair, M. S., Yu, J., Chan, J., Wang, M., Cerutti, G., Li, Z., Castagna, C., Corredor, L., Chu, H., Yuan, S., Poon, V., Chan, C., Chen, Z., Luo, Y., Cunningham, M., Chavez, A., Yin, M., Perlin, D., Tsuji, M., Yuen, K.-Y., Kwong, P., Sheng, Z., Huang, Y., Shapiro, L., Ho, D. D.. 2021-12-14. Isolation and comparative analysis of antibodies that broadly neutralize sarbecoviruses. https://doi.org/10.1101/2021.12.11.472236

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