Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose
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Significance: To respond better to evolving pathogens, sudden outbreaks, and individual patient needs, a flexible, safe, and efficient vaccine platform amenable to rapid production near the point of care is required. To this end, we created a fully synthetic, single-dose, adjuvant-free nanoparticle vaccine platform wherein modified dendrimer molecules nanoencapsulate antigen-expressing replicon mRNAs. Vaccines can be multiplexed and formed with multiple antigen-expressing replicons. After a single immunization, the rapid-production, contaminant-free vaccines elicit vital CD8 + T-cell and antibody responses that fully protect against lethal exposures to several deadly pathogens, including Ebola virus, H1N1 influenza, and Toxoplasma gondii . We believe this technology may allow for rapid-response vaccines with broad efficacy that reduce the number and frequency of vaccinations, and healthcare worker burden.
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One mRNA vaccine demonstrated efficacy in mice upon delivery of an unmodified, self-amplifying mRNA encoding the EBOV glycoprotein in a poly(amidoamine) dendrimer nanoparticle.
“One mRNA vaccine has demonstrated efficacy in mice upon delivery of an unmodified, self-amplifying mRNA encoding the EBOV glycoprotein (Fig. 4) in a poly(amidoamine) dendrimer nanoparticle.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [184]
The vaccine elicited glycoprotein-specific IgG antibodies and robust expression of IFNγ and IL-2 by CD8+ and CD4+ T cells, and two dosing regimens (two 4 μg doses or one 40 μg dose) protected mice from a lethal challenge.
“The vaccine elicited glycoprotein-specific IgG antibodies and robust expression of IFNγ and IL-2 by CD8+ and CD4+ T cells, and two dosing regimens (two 4 μg doses or one 40 μg dose) protected mice from a lethal challenge184.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [184]
Charge-altering releasable transporters and modified dendrimers can effectively deliver mRNA molecules in vitro and in vivo.
“In addition, charge-altering releasable transporters162,247 and modified dendrimers248 can effectively deliver mRNA molecules in vitro and in vivo.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [248]
Animals treated with mRNA nanoparticles produced antibody-based and CD8+ T-cell immune responses, and were completely protected from lethal challenges of Ebola virus, H1N1 influenza and Toxoplasma gondii.
“Animals treated with mRNA nanoparticles produced antibody-based and CD8 + T-cell immune responses, and were completely protected from lethal challenges of Ebola virus, H1N1 influenza and Toxoplasma gondii .”
From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [75]
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- Authors
- Chahal, J. S., Khan, O. F., Cooper, C. L., McPartlan, J. S., Tsosie, J. K., Tilley, L. D., Sidik, S. M., Lourido, S., Langer, R., Bavari, S., Ploegh, H. L., & Anderson, D. G.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Koch Institute for Integrative Cancer Research At MIT (US)
- United States Army Medical Research Institute of Infectious Diseases (US)
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-07-05
- Volume
- 113
- Issue
- 29
- Pages
- E4133-42
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4961123
- OpenAlex
- W2461517514
- Cited by
- 414
- References
- 105
- Citations by year
- 2026: 16 · 2025: 38 · 2024: 28 · 2023: 55 · 2022: 60 · 2021: 72 · 2020: 48 · 2019: 33 · 2018: 31 · 2017: 30 · 2016: 3
- FWCI
- 19.61
- Type
- journal article
- Language
- en
- Update notices
- correction (2016-08-22)
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
- Defense Threat Reduction Agency
- U.S. Army Medical Research Institute of Infectious Diseases
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- dendrimer nanoparticles, mRNA vaccines, adjuvant-free vaccine, Ebola virus, H1N1 influenza, Toxoplasma gondii, single-dose vaccine, CD8+ T cell responses, antibody response
- MeSH terms
- Animals, Cell Line, Female, HeLa Cells, Humans, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Orthomyxoviridae Infections, RNA, T-Lymphocytes, Toxoplasma, Toxoplasmosis, Vaccines, Hemorrhagic Fever, Ebola, Ebolavirus, Dendrimers, Rats, Influenza A Virus, H1N1 Subtype, Nanoparticles
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