Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail

Hansen, Johanna; Baum, Alina; Pascal, Kristen E.; Russo, Vincenzo; Giordano, Stephanie; Wloga, Elzbieta; Fulton, Benjamin O.; Yan, Ying; Koon, Katrina; Patel, Krunal; Chung, Kyung Min; Hermann, Aynur; Ullman, Erica; Cruz, Jonathan; Rafique, Ashique; Huang, Tammy; Fairhurst, Jeanette; Libertiny, Christen; Malbec, Marine; Lee, Wen-yi; Welsh, Richard; Farr, Glen; Pennington, Seth; Deshpande, Dipali; Cheng, Jemmie; Watty, Anke; Bouffard, Pascal; Babb, Robert; Levenkova, Natasha; Chen, Calvin; Zhang, Bojie; Romero Hernandez, Annabel; Saotome, Kei; Zhou, Yi; Franklin, Matthew; Sivapalasingam, Sumathi; Lye, David Chien; Weston, Stuart; Logue, James; Haupt, Robert; Frieman, Matthew; Chen, Gang; Olson, William; Murphy, Andrew J.; Stahl, Neil; Yancopoulos, George D.; Kyratsous, Christos A.

Neutralizing antibodies have become an important tool in treating infectious diseases. Recently, two separate approaches yielded successful antibody treatments for Ebola – one from genetically-humanized mice, and the other from a human survivor. Here, we describe parallel efforts using both humanized mice and convalescent patients to generate antibodies against the SARS-CoV-2 spike protein, yielding a large collection of fully-human antibodies that were characterized for binding, neutralization and three dimensional structure. Based on these criteria, we selected pairs of highly-potent individual antibodies that simultaneously bind the receptor-binding domain of the spike protein, providing ideal partners for a therapeutic antibody cocktail that aims to decrease the potential for virus escape mutants that might arise in response to selective pressure from a single antibody treatment.