| Literature DB >> 33655252 |
Lingshu Wang1, Tongqing Zhou1, Yi Zhang1, Eun Sung Yang1, Chaim A Schramm1, Wei Shi1, Amarendra Pegu1, Olamide K Oloninyi1, Amy Ransier1, Samuel Darko1, Sandeep R Narpala1, Christian Hatcher1, David R Martinez2,3, Yaroslav Tsybovsky4, Emily Phung1, Olubukola M Abiona1, Evan M Cale1, Lauren A Chang1, Kizzmekia S Corbett1, Anthony T DiPiazza1, Ingelise J Gordon1, Kwanyee Leung1, Tracy Liu1, Rosemarie D Mason1, Alexandra Nazzari1, Laura Novik1, Adam S Olia1, Nicole A Doria-Rose1, Tyler Stephens4, Christopher D Stringham1, Chloe Adrienna Talana1, I-Ting Teng1, Danielle Wagner1, Alicia T Widge1, Baoshan Zhang1, Mario Roederer1, Julie E Ledgerwood1, Tracy J Ruckwardt1, Martin R Gaudinski1, Ralph S Baric2,3, Barney S Graham1, Adrian B McDermott1, Daniel C Douek1, Peter D Kwong1, John R Mascola1, Nancy J Sullivan1, John Misasi1.
Abstract
The emergence of highly transmissible SARS-CoV-2 variants of concern (VOC) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. We identify four receptor-binding domain targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 12 variants including the B.1.1.7 and B.1.351 VOCs. Two of them are ultrapotent, with sub-nanomolar neutralization titers (IC50 <0.0006 to 0.0102 μ g/mL; IC80 < 0.0006 to 0.0251 μ g/mL). 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 potential means to mitigate resistance development. These results define the basis of therapeutic cocktails against VOCs and suggest that targeted boosting of existing immunity may increase vaccine breadth against VOCs.Entities:
Year: 2021 PMID： 33655252 PMCID： PMC7924272 DOI： 10.1101/2021.02.25.432969
Source DB: PubMed Journal: bioRxiv