The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates.
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.
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https://hdl.handle.net/10161/25007Published Version (Please cite this version)
10.1101/2020.12.31.424729Publication Info
(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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Show full item recordScholars@Duke
Priyamvada Acharya
Associate Professor in Surgery
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
Sophie Gobeil
Research Associate, Senior
Duke Human Vaccine Institute, Acharya Lab, Division of Structural Biology
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,
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
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
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
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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