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

被引:881
作者
Hansen, Johanna [1 ]
Baum, Alina [1 ]
Pascal, Kristen E. [1 ]
Russo, Vincenzo [1 ]
Giordano, Stephanie [1 ]
Wloga, Elzbieta [1 ]
Fulton, Benjamin O. [1 ]
Yan, Ying [1 ]
Koon, Katrina [1 ]
Patel, Krunal [1 ]
Chung, Kyung Min [1 ]
Hermann, Aynur [1 ]
Ullman, Erica [1 ]
Cruz, Jonathan [1 ]
Rafique, Ashique [1 ]
Huang, Tammy [1 ]
Fairhurst, Jeanette [1 ]
Libertiny, Christen [1 ]
Malbec, Marine [1 ]
Lee, Wen-yi [1 ]
Welsh, Richard [1 ]
Farr, Glen [1 ]
Pennington, Seth [1 ]
Deshpande, Dipali [1 ]
Cheng, Jemmie [1 ]
Watty, Anke [1 ]
Bouffard, Pascal [1 ]
Babb, Robert [1 ]
Levenkova, Natasha [1 ]
Chen, Calvin [1 ]
Zhang, Bojie [1 ]
Hernandez, Annabel Romero [1 ]
Saotome, Kei [1 ]
Zhou, Yi [1 ]
Franklin, Matthew [1 ]
Sivapalasingam, Sumathi [1 ]
Lye, David Chien [2 ]
Weston, Stuart [3 ]
Logue, James [3 ]
Haupt, Robert [3 ]
Frieman, Matthew [3 ]
Chen, Gang [1 ]
Olson, William [1 ]
Murphy, Andrew J. [1 ]
Stahl, Neil [1 ]
Yancopoulos, George D. [1 ]
Kyratsous, Christos A. [1 ]
机构
[1] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA
[2] Tan Tock Seng Hosp, Natl Ctr Infect Dis, Yong Loo Lin Sch Med, Lee Kong Chian Sch Med, 16 Jalan Tan Tock Seng, Singapore 308442, Singapore
[3] Univ Maryland, Dept Microbiol & Immunol, Sch Med, Baltimore, MD 21201 USA
关键词
CRYO-EM STRUCTURE; IMMUNOGLOBULIN GENES; VIRUS; MONOTHERAPY; CONTRIBUTE; SPIKE;
D O I
10.1126/science.abd0827
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1010 / +
页数:37
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