Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail
Johanna K. Hansen, Alina Baum, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Elzbieta Wloga, Benjamin O. Fulton, Ying Yan, Katrina Koon, Krunal Patel, Kyung Min Chung, Aynur Hermann, Erica Ullman, Jonathan W. Cruz, Ashique Rafique, Tammy Huang, Jeanette Fairhurst, Christen Libertiny, Marine Malbec, Wen‐Yi Lee, Richard S. Welsh, Glen A. Farr, Seth Pennington, Dipali Deshpande, Jemmie Cheng, Anke Watty, Pascal Bouffard, Robert Babb, Natasha Levenkova, Calvin Chen, Bojie Zhang, Annabel Romero Hernandez, Kei Saotome, Yi Zhou, Matthew C. Franklin, Sumathi Sivapalasingam, David Chien Lye, Stuart Weston, James Logue, Robert Haupt, Matthew B. Frieman, Gang Chen, William C. Olson, Andrew Murphy, Neil Stahl, George D. Yancopoulos, Christos A. Kyratsous
Abstract
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 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, which yielded a large collection of fully human antibodies that were characterized for binding, neutralization, and three-dimensional structure. On the basis of these criteria, we selected pairs of highly potent individual antibodies that simultaneously bind the receptor binding domain of the spike protein, thereby 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.