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

Johanna K. Hansen(Regeneron (United States)), Alina Baum(Regeneron (United States)), Kristen E. Pascal(Regeneron (United States)), Vincenzo Russo(Regeneron (United States)), Stephanie Giordano(Regeneron (United States)), Elzbieta Wloga(Regeneron (United States)), Benjamin O. Fulton(Regeneron (United States)), Ying Yan(Regeneron (United States)), Katrina Koon(Regeneron (United States)), Krunal Patel(Regeneron (United States)), Kyung Min Chung(Regeneron (United States)), Aynur Hermann(Regeneron (United States)), Erica Ullman(Regeneron (United States)), Jonathan W. Cruz(Regeneron (United States)), Ashique Rafique(Regeneron (United States)), Tammy Huang(Regeneron (United States)), Jeanette Fairhurst(Regeneron (United States)), Christen Libertiny(Regeneron (United States)), Marine Malbec(Regeneron (United States)), Wen‐Yi Lee(Regeneron (United States)), Richard S. Welsh(Regeneron (United States)), Glen A. Farr(Regeneron (United States)), Seth Pennington(Regeneron (United States)), Dipali Deshpande(Regeneron (United States)), Jemmie Cheng(Regeneron (United States)), Anke Watty(Regeneron (United States)), Pascal Bouffard(Regeneron (United States)), Robert Babb(Regeneron (United States)), Natasha Levenkova(Regeneron (United States)), Calvin Chen(Regeneron (United States)), Bojie Zhang(Regeneron (United States)), Annabel Romero Hernandez(Regeneron (United States)), Kei Saotome(Regeneron (United States)), Yi Zhou(Regeneron (United States)), Matthew C. Franklin(Regeneron (United States)), Sumathi Sivapalasingam(Regeneron (United States)), David Chien Lye(Tan Tock Seng Hospital), Stuart Weston(University of Maryland, Baltimore), James Logue(University of Maryland, Baltimore), Robert Haupt(University of Maryland, Baltimore), Matthew B. Frieman(University of Maryland, Baltimore), Gang Chen(Regeneron (United States)), William C. Olson(Regeneron (United States)), Andrew Murphy(Regeneron (United States)), Neil Stahl(Regeneron (United States)), George D. Yancopoulos(Regeneron (United States)), Christos A. Kyratsous(Regeneron (United States))
Science
June 15, 2020
Cited by 1,427Open Access
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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.


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