title: Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose.
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.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
authors.forename: Jasdave S
authors.initials: JS
authors.lastname: Chahal
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Omar F
authors.initials: OF
authors.lastname: Khan
authors.affiliation: Molecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702;
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Cooper
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
authors.forename: Justine S
authors.initials: JS
authors.lastname: McPartlan
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Tsosie
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
authors.forename: Lucas D
authors.initials: LD
authors.lastname: Tilley
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
authors.forename: Saima M
authors.initials: SM
authors.lastname: Sidik
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
authors.forename: Sebastian
authors.identifier: 0000-0002-5237-1095
authors.initials: S
authors.lastname: Lourido
authors.affiliation: 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.
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.affiliation: Molecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702;
authors.forename: Sina
authors.initials: S
authors.lastname: Bavari
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
authors.forename: Hidde L
authors.initials: HL
authors.lastname: Ploegh
authors.affiliation: 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.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Anderson
mesh_terms: D000818:Animals; D002460:Cell Line; D050091:Dendrimers / Q000627:therapeutic use*; D029043:Ebolavirus / Q000187:drug effects; D005260:Female; D006367:HeLa Cells; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053758:Nanoparticles / Q000627:therapeutic use*; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D012313:RNA / Q000627:therapeutic use*; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology; D014122:Toxoplasma / Q000187:drug effects; D014123:Toxoplasmosis / Q000517:prevention & control; D014612:Vaccines
chemical_list: D050091:Dendrimers; D014612:Vaccines; D012313:RNA
keywords: nanoparticle; parasites; replicon; vaccine platform; viruses