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Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail.
Science. 2020 08 21; 369(6506):1010-1014.Sci

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.

Authors+Show Affiliations

Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.National Centre for Infectious Diseases, Tan Tock Seng Hospital, Yong Loo Lin School of Medicine, Lee Kong Chian School of Medicine, 16 Jalan Tan Tock Seng, Singapore 308442, Singapore.Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA. christos.kyratsous@regeneron.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32540901

Citation

Hansen, Johanna, et al. "Studies in Humanized Mice and Convalescent Humans Yield a SARS-CoV-2 Antibody Cocktail." Science (New York, N.Y.), vol. 369, no. 6506, 2020, pp. 1010-1014.
Hansen J, Baum A, Pascal KE, et al. Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science. 2020;369(6506):1010-1014.
Hansen, J., Baum, A., Pascal, K. E., Russo, V., Giordano, S., Wloga, E., Fulton, B. O., Yan, Y., Koon, K., Patel, K., Chung, K. M., Hermann, A., Ullman, E., Cruz, J., Rafique, A., Huang, T., Fairhurst, J., Libertiny, C., Malbec, M., ... Kyratsous, C. A. (2020). Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science (New York, N.Y.), 369(6506), 1010-1014. https://doi.org/10.1126/science.abd0827
Hansen J, et al. Studies in Humanized Mice and Convalescent Humans Yield a SARS-CoV-2 Antibody Cocktail. Science. 2020 08 21;369(6506):1010-1014. PubMed PMID: 32540901.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. AU - Hansen,Johanna, AU - Baum,Alina, AU - Pascal,Kristen E, AU - Russo,Vincenzo, AU - Giordano,Stephanie, AU - Wloga,Elzbieta, AU - Fulton,Benjamin O, AU - Yan,Ying, AU - Koon,Katrina, AU - Patel,Krunal, AU - Chung,Kyung Min, AU - Hermann,Aynur, AU - Ullman,Erica, AU - Cruz,Jonathan, AU - Rafique,Ashique, AU - Huang,Tammy, AU - Fairhurst,Jeanette, AU - Libertiny,Christen, AU - Malbec,Marine, AU - Lee,Wen-Yi, AU - Welsh,Richard, AU - Farr,Glen, AU - Pennington,Seth, AU - Deshpande,Dipali, AU - Cheng,Jemmie, AU - Watty,Anke, AU - Bouffard,Pascal, AU - Babb,Robert, AU - Levenkova,Natasha, AU - Chen,Calvin, AU - Zhang,Bojie, AU - Romero Hernandez,Annabel, AU - Saotome,Kei, AU - Zhou,Yi, AU - Franklin,Matthew, AU - Sivapalasingam,Sumathi, AU - Lye,David Chien, AU - Weston,Stuart, AU - Logue,James, AU - Haupt,Robert, AU - Frieman,Matthew, AU - Chen,Gang, AU - Olson,William, AU - Murphy,Andrew J, AU - Stahl,Neil, AU - Yancopoulos,George D, AU - Kyratsous,Christos A, Y1 - 2020/06/15/ PY - 2020/05/30/received PY - 2020/06/11/accepted PY - 2020/6/17/pubmed PY - 2020/9/2/medline PY - 2020/6/17/entrez SP - 1010 EP - 1014 JF - Science (New York, N.Y.) JO - Science VL - 369 IS - 6506 N2 - 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. SN - 1095-9203 UR - https://www.unboundmedicine.com/medline/citation/32540901/Studies_in_humanized_mice_and_convalescent_humans_yield_a_SARS_CoV_2_antibody_cocktail_ L2 - https://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=32540901 DB - PRIME DP - Unbound Medicine ER -