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Proc Natl Acad Sci U S A. 2016 Jul 19;113(29):E4133-42. doi: 10.1073/pnas.1600299113. Epub 2016 Jul 5.

Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose.

Author information

1
Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
2
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
3
Molecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702;
4
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139; Harvard-MIT Division of Health Science and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139.
5
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Molecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139; Harvard-MIT Division of Health Science and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139 dgander@mit.edu.

Abstract

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.

KEYWORDS:

nanoparticle; parasites; replicon; vaccine platform; viruses

PMID:
27382155
PMCID:
PMC4961123
DOI:
10.1073/pnas.1600299113
[Indexed for MEDLINE]
Free PMC Article

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