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
Mihai Luchian Azoitei
Assistant Professor in Medicine
Thomas Norton Denny
Professor in Medicine
Thomas N. Denny, MSc, M.Phil, is the Chief Operating Officer of the Duke Human Vaccine
Institute (DHVI) and the Center for HIV/AIDS Vaccine Immunology (CHAVI), 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. He has recently been
appointed to the Duke University Fuqua School of Business Health Sector Advisory Council.
Previously, he was an Associate Professor of Pathology, Laboratory M
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
The Haynes lab is studying host innate and adaptive immune responses to the human
immunodeficiency virus (HIV), tuberculosis (TB), and influenza in order to find the
enabling technology to make preventive vaccines against these three major infectious
diseases. Mucosal Immune Responses in Acute HIV Infection The Haynes lab is working
to determine why broadly neutralizing antibodies are rarely made in acute HIV infection
(AHI), currently a major obstacle in the de
Dapeng Li
Medical Instructor in the Department of Medicine
David Charles Montefiori
Professor in Surgery
Dr. Montefiori is Professor and Director of the Laboratory for AIDS Vaccine Research
and Development in the Department of Surgery, Division of Surgical Sciences, Duke
University Medical Center. His major research interests are viral immunology and AIDS
vaccine development, with a special emphasis on neutralizing antibodies. One of his
highest priorities is to identify immunogens that generate broadly cross-reactive
neutralizing antibodies for inclusion in HIV vaccines. Many aspects of the
Kevin O'Neil Saunders
Associate Professor in Surgery
The Saunders laboratory aims to understand the immunology of HIV-1 antibodies and
the molecular biology of their interaction with HIV-1 envelope (Env) glycoprotein.
Our overall goal is to develop protective antibody-based vaccines; therefore, the
laboratory has two sections–antibody repertoire analysis and immunogen design.
Our research premise is that vaccine-elicited antibodies will broadly neutralize HIV-1
if they can bind directly to the host glycans on Env. However, Env glycans are
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
Associate Professor in Medicine
Christopher Wildrick Woods
Professor of Medicine
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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