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Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model.
Science. 2020 08 21; 369(6506):956-963.Sci

Abstract

Countermeasures to prevent and treat coronavirus disease 2019 (COVID-19) are a global health priority. We enrolled a cohort of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-recovered participants, developed neutralization assays to investigate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen more than 1800 antibodies, and established an animal model to test protection. We isolated potent neutralizing antibodies (nAbs) to two epitopes on the receptor binding domain (RBD) and to distinct non-RBD epitopes on the spike (S) protein. As indicated by maintained weight and low lung viral titers in treated animals, the passive transfer of a nAb provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs also define protective epitopes to guide vaccine design.

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Authors+Show Affiliations

Rogers TF
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Zhao F
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Huang D
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Beutler N
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Burns A
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
He WT
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Limbo O
IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI, New York, NY 10004, USA.
Smith C
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Song G
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Woehl J
IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI, New York, NY 10004, USA.
Yang L
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Abbott RK
Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA. Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.
Callaghan S
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Garcia E
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Hurtado J
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA. Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Parren M
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Peng L
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Ramirez S
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.
Ricketts J
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Ricciardi MJ
Department of Pathology, George Washington University, Washington, DC 20052, USA.
Rawlings SA
Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Wu NC
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Yuan M
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Smith DM
Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Nemazee D
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Teijaro JR
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Voss JE
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Wilson IA
IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Andrabi R
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Briney B
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA. Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Landais E
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI, New York, NY 10004, USA.
Sok D
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. dsok@iavi.org jjardine@iavi.org burton@scripps.edu. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI, New York, NY 10004, USA.
Jardine JG
IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. dsok@iavi.org jjardine@iavi.org burton@scripps.edu. IAVI, New York, NY 10004, USA.
Burton DR
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. dsok@iavi.org jjardine@iavi.org burton@scripps.edu. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA. Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA.

MeSH

AdultAngiotensin-Converting Enzyme 2AnimalsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralAntibody AffinityAntibody SpecificityBetacoronavirusBinding SitesCOVID-19Cell LineCoronavirus InfectionsDisease Models, AnimalEpitopesFemaleHumansImmunization, PassiveLungMaleMesocricetusMiddle AgedNeutralization TestsPandemicsPeptidyl-Dipeptidase APneumonia, ViralProtein DomainsSARS-CoV-2Spike Glycoprotein, CoronavirusViral LoadVirus Replication

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

32540903

Citation

Rogers, Thomas F., et al. "Isolation of Potent SARS-CoV-2 Neutralizing Antibodies and Protection From Disease in a Small Animal Model." Science (New York, N.Y.), vol. 369, no. 6506, 2020, pp. 956-963.
Rogers TF, Zhao F, Huang D, et al. Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Science. 2020;369(6506):956-963.
Rogers, T. F., Zhao, F., Huang, D., Beutler, N., Burns, A., He, W. T., Limbo, O., Smith, C., Song, G., Woehl, J., Yang, L., Abbott, R. K., Callaghan, S., Garcia, E., Hurtado, J., Parren, M., Peng, L., Ramirez, S., Ricketts, J., ... Burton, D. R. (2020). Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Science (New York, N.Y.), 369(6506), 956-963. https://doi.org/10.1126/science.abc7520
Rogers TF, et al. Isolation of Potent SARS-CoV-2 Neutralizing Antibodies and Protection From Disease in a Small Animal Model. Science. 2020 08 21;369(6506):956-963. PubMed PMID: 32540903.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. AU - Rogers,Thomas F, AU - Zhao,Fangzhu, AU - Huang,Deli, AU - Beutler,Nathan, AU - Burns,Alison, AU - He,Wan-Ting, AU - Limbo,Oliver, AU - Smith,Chloe, AU - Song,Ge, AU - Woehl,Jordan, AU - Yang,Linlin, AU - Abbott,Robert K, AU - Callaghan,Sean, AU - Garcia,Elijah, AU - Hurtado,Jonathan, AU - Parren,Mara, AU - Peng,Linghang, AU - Ramirez,Sydney, AU - Ricketts,James, AU - Ricciardi,Michael J, AU - Rawlings,Stephen A, AU - Wu,Nicholas C, AU - Yuan,Meng, AU - Smith,Davey M, AU - Nemazee,David, AU - Teijaro,John R, AU - Voss,James E, AU - Wilson,Ian A, AU - Andrabi,Raiees, AU - Briney,Bryan, AU - Landais,Elise, AU - Sok,Devin, AU - Jardine,Joseph G, AU - Burton,Dennis R, Y1 - 2020/06/15/ PY - 2020/05/12/received PY - 2020/06/11/accepted PY - 2020/6/17/pubmed PY - 2020/9/2/medline PY - 2020/6/17/entrez SP - 956 EP - 963 JF - Science (New York, N.Y.) JO - Science VL - 369 IS - 6506 N2 - Countermeasures to prevent and treat coronavirus disease 2019 (COVID-19) are a global health priority. We enrolled a cohort of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-recovered participants, developed neutralization assays to investigate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen more than 1800 antibodies, and established an animal model to test protection. We isolated potent neutralizing antibodies (nAbs) to two epitopes on the receptor binding domain (RBD) and to distinct non-RBD epitopes on the spike (S) protein. As indicated by maintained weight and low lung viral titers in treated animals, the passive transfer of a nAb provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs also define protective epitopes to guide vaccine design. SN - 1095-9203 UR - https://www.unboundmedicine.com/medline/citation/32540903/Isolation_of_potent_SARS_CoV_2_neutralizing_antibodies_and_protection_from_disease_in_a_small_animal_model_ L2 - https://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=32540903 DB - PRIME DP - Unbound Medicine ER -