Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.
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 articleSubject
TracheaAnimals
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
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https://hdl.handle.net/10161/25005Published Version (Please cite this version)
10.1038/s41586-021-03594-0Publication 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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Show full item recordScholars@Duke
Priyamvada Acharya
Associate Professor in Surgery
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
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
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
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.
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,
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
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
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
Alphabetical list of authors with Scholars@Duke profiles.

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