Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants

The emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. We identified four receptor binding domain–targeting antibodies from three early-outbreak convalescent...

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Detalles Bibliográficos
Autores principales: Wang, Lingshu, Zhou, Tongqing, Zhang, Yi, Yang, Eun Sung, Schramm, Chaim A., Shi, Wei, Pegu, Amarendra, Oloniniyi, Olamide K., Henry, Amy R., Darko, Samuel, Narpala, Sandeep R., Hatcher, Christian, Martinez, David R., Tsybovsky, Yaroslav, Phung, Emily, Abiona, Olubukola M., Antia, Avan, Cale, Evan M., Chang, Lauren A., Choe, Misook, Corbett, Kizzmekia S., Davis, Rachel L., DiPiazza, Anthony T., Gordon, Ingelise J., Hait, Sabrina Helmold, Hermanus, Tandile, Kgagudi, Prudence, Laboune, Farida, Leung, Kwanyee, Liu, Tracy, Mason, Rosemarie D., Nazzari, Alexandra F., Novik, Laura, O’Connell, Sarah, O’Dell, Sijy, Olia, Adam S., Schmidt, Stephen D., Stephens, Tyler, Stringham, Christopher D., Talana, Chloe Adrienna, Teng, I-Ting, Wagner, Danielle A., Widge, Alicia T., Zhang, Baoshan, Roederer, Mario, Ledgerwood, Julie E., Ruckwardt, Tracy J., Gaudinski, Martin R., Moore, Penny L., Doria-Rose, Nicole A., Baric, Ralph S., Graham, Barney S., McDermott, Adrian B., Douek, Daniel C., Kwong, Peter D., Mascola, John R., Sullivan, Nancy J., Misasi, John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9269068/
https://www.ncbi.nlm.nih.gov/pubmed/34210892
http://dx.doi.org/10.1126/science.abh1766
Descripción
Sumario:The emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. We identified four receptor binding domain–targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 23 variants, including the B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, and B.1.617 VOCs. Two antibodies are ultrapotent, with subnanomolar neutralization titers [half-maximal inhibitory concentration (IC(50)) 0.3 to 11.1 nanograms per milliliter; IC(80) 1.5 to 34.5 nanograms per milliliter). We define the structural and functional determinants of binding for all four VOC-targeting antibodies and show that combinations of two antibodies decrease the in vitro generation of escape mutants, suggesting their potential in mitigating resistance development.

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