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The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates.

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Date
2021-02-18
Authors
Li, Dapeng
Edwards, Robert J
Manne, Kartik
Martinez, David R
Schäfer, Alexandra
Alam, S Munir
Wiehe, Kevin
Lu, Xiaozhi
Parks, Robert
Sutherland, Laura L
Oguin, Thomas H
McDanal, Charlene
Perez, Lautaro G
Mansouri, Katayoun
Gobeil, Sophie MC
Janowska, Katarzyna
Stalls, Victoria
Kopp, Megan
Cai, Fangping
Lee, Esther
Foulger, Andrew
Hernandez, Giovanna E
Sanzone, Aja
Tilahun, Kedamawit
Jiang, Chuancang
Tse, Longping V
Bock, Kevin W
Minai, Mahnaz
Nagata, Bianca M
Cronin, Kenneth
Gee-Lai, Victoria
Deyton, Margaret
Barr, Maggie
Holle, Tarra Von
Macintyre, Andrew N
Stover, Erica
Feldman, Jared
Hauser, Blake M
Caradonna, Timothy M
Scobey, Trevor D
Rountree, Wes
Wang, Yunfei
Moody, M Anthony
Cain, Derek W
DeMarco, C Todd
Denny, ThomasN
Woods, Christopher W
Petzold, Elizabeth W
Schmidt, Aaron G
Teng, I-Ting
Zhou, Tongqing
Kwong, Peter D
Mascola, John R
Graham, Barney S
Moore, Ian N
Seder, Robert
Andersen, Hanne
Lewis, Mark G
Montefiori, David C
Sempowski, Gregory D
Baric, Ralph S
Acharya, Priyamvada
Haynes, Barton F
Saunders, Kevin O
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Abstract
SARS-CoV-2 neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) and the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV-1 infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of binding. Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infection in vitro , while five non-neutralizing NTD antibodies mediated FcγR-independent in vitro infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Nonetheless, three of 31 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo , increased lung inflammation can occur in SARS-CoV-2 antibody-infused macaques.
Type
Journal article
Permalink
https://hdl.handle.net/10161/25007
Published Version (Please cite this version)
10.1101/2020.12.31.424729
Publication Info
Li, Dapeng; Edwards, Robert J; Manne, Kartik; Martinez, David R; Schäfer, Alexandra; Alam, S Munir; ... Saunders, Kevin O (2021). The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates. bioRxiv. 10.1101/2020.12.31.424729. Retrieved from https://hdl.handle.net/10161/25007.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Acharya

Priyamvada Acharya

Associate Professor in Surgery
Denny

Thomas Norton Denny

Professor in Medicine
Thomas N. Denny, MSc, M.Phil, is the Chief Operating Officer of the Duke Human Vaccine Institute (DHVI), Associate Dean for Duke Research and Discovery @RTP, and a Professor of Medicine in the Department of Medicine at Duke University Medical Center. He is also an Affiliate Member of the Duke Global Health Institute. Previously, he served on the Health Sector Advisory Council of the Duke University Fuquay School of Business. Prior to joining Duke, he was an Associate Professor of Pathology, Labo
Gobeil

Sophie Gobeil

Research Associate, Senior
Duke Human Vaccine Institute, Acharya Lab, Division of Structural Biology
Montefiori

David Charles Montefiori

Professor in Surgery
Dr. Montefiori is Professor and Director of the Laboratory for HIV and COVID-19 Vaccine Research & Development in the Department of Surgery, Division of Surgical Sciences at Duke University Medical Center. His major research interests are viral immunology and HIV and COVID-19 vaccine development, with a special emphasis on neutralizing antibodies. Multiple aspects of HIV-1 neutralizing antibodies are studied in his laboratory, including mechanisms of neutralization and escape,
Moody

Michael Anthony Moody

Professor of Pediatrics
Tony Moody, MD is a Professor in the Department of Pediatrics, Division of Infectious Diseases and Professor in the Department of Integrative Immunobiology at Duke University Medical Center. Research in the Moody lab is focused on understanding the B cell responses during infection, vaccination, and disease. The lab has become a resource for human phenotyping, flow characterization, staining and analysis at the Duke Human Vaccine Institute (DHVI). The Moody lab is currently funded to study in
Saunders

Kevin O'Neil Saunders

Associate Professor in Surgery
Dr. Kevin O. Saunders graduated from Davidson College in 2005 with a bachelor of science in biology. At Davidson College, he trained in the laboratory of Dr. Karen Hales identifying the genetic basis of infertility. Dr. Saunders completed his doctoral research on CD8+ T cell immunity against HIV-1 infection with Dr. Georgia Tomaras at Duke University in 2010. He subsequently trained as a postdoctoral fellow in the laboratories of Drs. Gary Nabel and John Mascola at the National Institutes of
Sempowski

Gregory David Sempowski

Professor in Medicine
Dr. Sempowski earned his PhD in Immunology from the University of Rochester and was specifically trained in the areas of inflammation, wound healing, and host response (innate and adaptive).  Dr. Sempowski contributed substantially to the field of lung inflammation and fibrosis defining the roles of pulmonary fibroblast heterogeneity and CD40/CD40L signaling in regulating normal and pathogenic lung inflammation.  During his postdoctoral training with Dr. Barton F. H
Woods

Christopher Wildrick Woods

Wolfgang Joklik Distinguished Professor of Global Health
1. Emerging Infections 2. Global Health 3. Epidemiology of infectious diseases 4. Clinical microbiology and diagnostics 5. Bioterrorism Preparedness 6. Surveillance for communicable diseases 7. Antimicrobial resistance
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