A Multi-Targeting, Nucleoside-Modified mRNA Influenza Virus Vaccine Provides Broad Protection in Mice
Open accessAbstract
Influenza viruses are respiratory pathogens of public health concern worldwide with up to 650,000 deaths occurring each year. Seasonal influenza virus vaccines are employed to prevent disease, but with limited effectiveness. Development of a universal influenza virus vaccine with the potential to elicit long-lasting, broadly cross-reactive immune responses is necessary for reducing influenza virus prevalence. In this study, we have utilized lipid nanoparticle-encapsulated, nucleoside-modified mRNA vaccines to intradermally deliver a combination of conserved influenza virus antigens (hemagglutinin stalk, neuraminidase, matrix-2 ion channel, and nucleoprotein) and induce strong immune responses with substantial breadth and potency in a murine model. The immunity conferred by nucleoside-modified mRNA-lipid nanoparticle vaccines provided protection from challenge with pandemic H1N1 virus at 500 times the median lethal dose after administration of a single immunization, and the combination vaccine protected from morbidity at a dose of 50 ng per antigen. The broad protective potential of a single dose of combination vaccine was confirmed by challenge with a panel of group 1 influenza A viruses. These findings support the advancement of nucleoside-modified mRNA-lipid nanoparticle vaccines expressing multiple conserved antigens as universal influenza virus vaccine candidates.
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A single mRNA vaccine can encode multiple antigens, strengthening the immune response against resilient pathogens.
“Moreover, a single mRNA vaccine can encode multiple antigens, strengthening the immune response against resilient pathogens7”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [7]
A 50 ng dose of nucleoside-modified mRNA encoding three conserved influenza proteins (neuraminidase, nucleoprotein and matrix-2 ion channel protein) in addition to the haemagglutinin stalk generated broadly protective antibodies and protected mice from a 500× LD50 viral challenge.
“Another study used LNPs to deliver a 50 ng dose of nucleoside-modified mRNA encoding three conserved influenza proteins: neuraminidase, nucleoprotein and matrix-2 ion channel protein (Fig. 4) in addition to the haemagglutinin stalk7. Incredibly, this minuscule mRNA dose generated broadly protective antibodies and protected mice from an extraordinarily large viral challenge (500× LD50).”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [7]
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- Authors
- Freyn, A. W., Ramos da Silva, J., Rosado, V. C., Bliss, C. M., Pine, M., Mui, B. L., Tam, Y. K., Madden, T. D., de Souza Ferreira, L. C., Weissman, D., Krammer, F., Coughlan, L., Palese, P., Pardi, N., & Nachbagauer, R.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- University of Pennsylvania (US)
- Acuitas Therapeutics (Canada) (CA)
- Corresponding author
- Pardi, Norbert
- Nachbagauer, Raffael
- ORCID
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2020-07
- Volume
- 28
- Issue
- 7
- Pages
- 1569-1584
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC7335735
- OpenAlex
- W3016394521
- Cited by
- 299
- References
- 67
- Citations by year
- 2026: 25 · 2025: 58 · 2024: 50 · 2023: 55 · 2022: 58 · 2021: 44 · 2020: 9
- FWCI
- 29.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo (2019/01523-3)
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (AI07647, 5P01AI097092-07, 75N93019C00051, R01-AI146101-01)
- U.S. Public Health Service (AI07647, 5P01AI097092-07)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- universal influenza vaccine, nucleoside-modified mRNA, lipid nanoparticle vaccine, multi-antigen vaccine, hemagglutinin stalk, neuraminidase, matrix protein 2, nucleocapsid protein, pandemic H1N1, immunological cross-reactivity, intradermal drug delivery
- MeSH terms
- mRNA Vaccines, Animals, Antibodies, Viral, Antigens, Viral, Disease Models, Animal, Influenza Vaccines, Injections, Intradermal, Liposomes, Neuraminidase, Nucleosides, Orthomyxoviridae Infections, Vaccines, Synthetic, Hemagglutinin Glycoproteins, Influenza Virus, Nucleocapsid Proteins, NIH 3T3 Cells, Mice, Influenza A Virus, H1N1 Subtype, Nanoparticles
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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