Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 113, Issue 29, Pages E4133-E4142Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1600299113
Keywords
nanoparticle; vaccine platform; replicon; viruses; parasites
Categories
Funding
- Department of Defense Office of Congressionally Directed Medical Research's Joint Warfighter Medical Research Program
- MediVector, Inc. [OSP 30-1765-9901]
- Ragon Institute Innovation Grant [OSP 39-1788-0101]
- Defense Threat Reduction Agency/Joint Science and Technology Office programs in vaccines and pretreatments
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Vaccines have had broad medical impact, but existing vaccine technologies and production methods are limited in their ability to respond rapidly to evolving and emerging pathogens, or sudden outbreaks. Here, we develop a rapid-response, fully synthetic, single-dose, adjuvant-free dendrimer nanoparticle vaccine platform wherein antigens are encoded by encapsulated mRNA replicons. To our knowledge, this system is the first capable of generating protective immunity against a broad spectrum of lethal pathogen challenges, including H1N1 influenza, Toxoplasma gondii, and Ebola virus. The vaccine can be formed with multiple antigen-expressing replicons, and is capable of eliciting both CD8(+) T-cell and antibody responses. The ability to generate viable, contaminant-free vaccines within days, to single or multiple antigens, may have broad utility for a range of diseases.
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