Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies
Open accessAbstract
Currently available influenza virus vaccines have inadequate effectiveness and are reformulated annually due to viral antigenic drift. Thus, development of a vaccine that confers long-term protective immunity against antigenically distant influenza virus strains is urgently needed. The highly conserved influenza virus hemagglutinin (HA) stalk represents one of the potential targets of broadly protective/universal influenza virus vaccines. Here, we evaluate a potent broadly protective influenza virus vaccine candidate that uses nucleoside-modified and purified mRNA encoding full-length influenza virus HA formulated in lipid nanoparticles (LNPs). We demonstrate that immunization with HA mRNA-LNPs induces antibody responses against the HA stalk domain of influenza virus in mice, rabbits, and ferrets. The HA stalk-specific antibody response is associated with protection from homologous, heterologous, and heterosubtypic influenza virus infection in mice.
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A primer-booster regimen of a lipid nanoparticle-based mRNA vaccine (30 μg) encoding the conserved haemagglutinin stalk from the Cal09 H1N1 strain produced a stalk-specific antibody response in mice, ferrets and rabbits.
“A primer–booster regimen of a LNP-based mRNA vaccine (30 µg) encoding the conserved haemagglutinin stalk from the Cal09 H1N1 strain produced a stalk-specific antibody response in mice, ferrets and rabbits149.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [149]
The broadly protective antibodies conferred homologous immunity against Cal09 H1N1, heterologous immunity against PR8 H1N1 and heterosubtypic immunity against H5N1 in mice and protected them against a lethal viral challenge.
“The broadly protective antibodies conferred homologous immunity against Cal09 H1N1, heterologous immunity against PR8 H1N1 and heterosubtypic immunity against H5N1 in mice and protected them against a lethal viral challenge149.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [149]
Novel strategies against HIV and influenza involve delivering mRNA vaccines that target conserved regions such as the haemagglutinin stalk on influenza, or encoding broadly neutralizing antibodies such as VRC01 that bind to conserved regions of the CD4 binding site on the HIV gp120 protein.
“Novel strategies against these viruses involve delivering mRNA vaccines that target conserved regions such as the haemagglutinin stalk on influenza149, or encodeing broadly neutralizing antibodies such as VRC01 that bind to conserved regions of the CD4 binding site on the HIV gp120 protein206.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [149]
Lipid nanoparticle-mRNA vaccines are being investigated as influenza vaccines, with some formulations in clinical trials.
“Lipid nanoparticle–mRNA vaccines are also being investigated as influenza vaccines29,41,156,157,159,184,189–191, with some formulations in clinical trials (Table 1).”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [189]
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References 50 · Cited by 281
- Authors
- Pardi, N., Parkhouse, K., Kirkpatrick, E., McMahon, M., Zost, S. J., Mui, B. L., Tam, Y. K., Karikó, K., Barbosa, C. J., Madden, T. D., Hope, M. J., Krammer, F., Hensley, S. E., & Weissman, D.
- Affiliations
- University of Pennsylvania (US)
- Icahn School of Medicine at Mount Sinai (US)
- Acuitas Therapeutics (Canada) (CA)
- BioNTech (Germany) (DE)
- Corresponding author
- Hensley, Scott E.
- Weissman, Drew
- ORCID
- Venue
- Nature Communications
- Published
- 2018-08-22
- Volume
- 9
- Issue
- 1
- Pages
- 3361-3361
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6105651
- OpenAlex
- W2885263529
- Cited by
- 281
- References
- 50
- Citations by year
- 2026: 25 · 2025: 37 · 2024: 41 · 2023: 26 · 2022: 38 · 2021: 57 · 2020: 33 · 2019: 22 · 2018: 1
- FWCI
- 21.97
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (AI109946, 1R01AI113047, 1R01AI108686, HHSN272201400005C, R01-AI124429, R01-AI084860)
- Burroughs Wellcome Fund (Pathogenesis of Infectious Disease Award)
- Takeda Pharmaceuticals U.S.A. (New Frontiers)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- influenza virus vaccine, hemagglutinin stalk, nucleoside-modified mRNA, lipid nanoparticles, universal influenza vaccine, heterosubtypic protection, antibody response, antigenic drift
- MeSH terms
- Animals, Antibodies, Viral, Cells, Cultured, Dogs, Enzyme-Linked Immunosorbent Assay, Female, Ferrets, Flow Cytometry, Hemagglutinins, Mice, Inbred BALB C, Orthomyxoviridae, Phylogeny, Rabbits, RNA, Messenger, Mice, Influenza A Virus, H5N1 Subtype, Madin Darby Canine Kidney Cells
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