Dendrimer-RNA Nanoparticles Generate Protective Immunity Against Lethal Ebola, H1N1 Influenza, and Toxoplasma Gondii Challenges With a Single Dose

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Dendrimers / therapeutic use*
  • Ebolavirus / drug effects
  • Female
  • HeLa Cells
  • Hemorrhagic Fever, Ebola / prevention & control
  • Humans
  • Influenza A Virus, H1N1 Subtype / drug effects
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nanoparticles / therapeutic use*
  • Orthomyxoviridae Infections / prevention & control
  • RNA / therapeutic use*
  • Rats
  • T-Lymphocytes / immunology
  • Toxoplasma / drug effects
  • Toxoplasmosis / prevention & control
  • Vaccines*

Substances

  • Dendrimers
  • Vaccines
  • RNA