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Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.

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Date
2021-06
Authors
Saunders, Kevin O
Lee, Esther
Parks, Robert
Martinez, David R
Li, Dapeng
Chen, Haiyan
Edwards, Robert J
Gobeil, Sophie
Barr, Maggie
Mansouri, Katayoun
Alam, S Munir
Sutherland, Laura L
Cai, Fangping
Sanzone, Aja M
Berry, Madison
Manne, Kartik
Bock, Kevin W
Minai, Mahnaz
Nagata, Bianca M
Kapingidza, Anyway B
Azoitei, Mihai
Tse, Longping V
Scobey, Trevor D
Spreng, Rachel L
Rountree, R Wes
DeMarco, C Todd
Denny, Thomas N
Woods, Christopher W
Petzold, Elizabeth W
Tang, Juanjie
Oguin, Thomas H
Sempowski, Gregory D
Gagne, Matthew
Douek, Daniel C
Tomai, Mark A
Fox, Christopher B
Seder, Robert
Wiehe, Kevin
Weissman, Drew
Pardi, Norbert
Golding, Hana
Khurana, Surender
Acharya, Priyamvada
Andersen, Hanne
Lewis, Mark G
Moore, Ian N
Montefiori, David C
Baric, Ralph S
Haynes, Barton F
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Abstract
Betacoronaviruses caused the outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, as well as the current pandemic of SARS coronavirus 2 (SARS-CoV-2)1-4. Vaccines that elicit protective immunity against SARS-CoV-2 and betacoronaviruses that circulate in animals have the potential to prevent future pandemics. Here we show that the immunization of macaques with nanoparticles conjugated with the receptor-binding domain of SARS-CoV-2, and adjuvanted with 3M-052 and alum, elicits cross-neutralizing antibody responses against bat coronaviruses, SARS-CoV and SARS-CoV-2 (including the B.1.1.7, P.1 and B.1.351 variants). Vaccination of macaques with these nanoparticles resulted in a 50% inhibitory reciprocal serum dilution (ID50) neutralization titre of 47,216 (geometric mean) for SARS-CoV-2, as well as in protection against SARS-CoV-2 in the upper and lower respiratory tracts. Nucleoside-modified mRNAs that encode a stabilized transmembrane spike or monomeric receptor-binding domain also induced cross-neutralizing antibody responses against SARS-CoV and bat coronaviruses, albeit at lower titres than achieved with the nanoparticles. These results demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses, and provide a multimeric protein platform for the further development of vaccines against multiple (or all) betacoronaviruses.
Type
Journal article
Subject
Trachea
Animals
Macaca
Humans
Common Cold
Disease Models, Animal
Viral Vaccines
Adjuvants, Immunologic
Vaccination
Administration, Intranasal
Cross Reactions
Models, Molecular
Female
Male
Nanoparticles
Antibodies, Neutralizing
Pandemics
Spike Glycoprotein, Coronavirus
Betacoronavirus
COVID-19
SARS-CoV-2
COVID-19 Vaccines
Permalink
https://hdl.handle.net/10161/25005
Published Version (Please cite this version)
10.1038/s41586-021-03594-0
Publication Info
Saunders, Kevin O; Lee, Esther; Parks, Robert; Martinez, David R; Li, Dapeng; Chen, Haiyan; ... Haynes, Barton F (2021). Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses. Nature, 594(7864). pp. 553-559. 10.1038/s41586-021-03594-0. Retrieved from https://hdl.handle.net/10161/25005.
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
Alam

S. Munir Alam

Professor in Medicine
Research Interests.  The Alam laboratory’s primary research is focused on understanding the biophysical properties of antigen-antibody binding and the molecular events of early B cell activation using the HIV-1 broadly neutralizing antibody (bnAb) lineage models. We are studying how HIV-1 Envelope proteins of varying affinities are sensed by B cells expressing HIV-1 bnAbs or their germline antigen receptors and initiate early signaling events for their activation. In the lon
Azoitei

Mihai Luchian Azoitei

Assistant Professor in Medicine
Dr. Mihai Azoitei obtained a BA in biochemistry and computer science from Middlebury College (Middlebury, Vermont) and a PhD in biochemistry from the University of Washington (Seattle, WA), where he worked in the group of Dr. William Schief. He then completed postdoctoral studies in the lab of Dr. Klaus Hahn in the Department of Pharmacology at the University of North Carolina at Chapel Hill before joining Duke University and the Duke Human Vaccine Institute as an assistant professor in 2018.<br
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
Haynes

Barton Ford Haynes

Frederic M. Hanes Distinguished Professor of Medicine
Barton F. Haynes, M.D. is the Frederic M. Hanes Professor of Medicine and Immunology, and Director of the Duke Human Vaccine Institute. Prior to leading the DHVI, Dr. Haynes served as Chief of the Division of Rheumatology, Allergy and Clinical Immunology, and later as Chair of the Department of Medicine. As Director of the Duke Human Vaccine Institute, Bart Haynes is leading a team of investigators working on vaccines for emerging infections, including tuberculosis, pandemic influenza, emergi

Dapeng Li

Medical Instructor in the Department of Medicine
This author no longer has a Scholars@Duke profile, so the information shown here reflects their Duke status at the time this item was deposited.
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,
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
Wiehe

Kevin J Wiehe

Norman L. Letvin Associate Professor in Medicine
Dr. Kevin Wiehe is the associate director of research, director of computational biology and co-director of the Quantitative Research Division at the Duke Human Vaccine Institute (DHVI). He has over 20 years of experience in the field of computational biology and has expertise in computational structural biology, computational genomics, and computational immunology. For the past decade, he has applied his unique background to developing computational approaches for studying the B cell
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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Alphabetical list of authors with Scholars@Duke profiles.
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