Development of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus
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Abstract
mRNA lipid nanoparticle (LNP) vaccines would be useful during an influenza virus pandemic since they can be produced rapidly and do not require the generation of egg-adapted vaccine seed stocks. Highly pathogenic avian influenza viruses from H5 clade 2.3.4.4b are circulating at unprecedently high levels in wild and domestic birds and have the potential to adapt to humans. Here, we generate an mRNA lipid nanoparticle (LNP) vaccine encoding the hemagglutinin (HA) glycoprotein from a clade 2.3.4.4b H5 isolate. The H5 mRNA-LNP vaccine elicits strong T cell and antibody responses in female mice, including neutralizing antibodies and broadly-reactive anti-HA stalk antibodies. The H5 mRNA-LNP vaccine elicits antibodies at similar levels compared to whole inactivated vaccines in female mice with and without prior H1N1 exposures. Finally, we find that the H5 mRNA-LNP vaccine is immunogenic in male ferrets and prevents morbidity and mortality of animals following 2.3.4.4b H5N1 challenge. Together, our data demonstrate that a monovalent mRNA-LNP vaccine expressing 2.3.4.4b H5 is immunogenic and protective in pre-clinical animal models.
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A recent report evaluating an mRNA-based vaccine expressing the A/Astrakhan HA reported 3-fold lower neutralizing titers against A/pheasant/New York/22-009066-001/2022 that more closely matches the currently circulating H5N1 circulating in the United States.
“A recent report evaluating an mRNA-based vaccine expressing the A/Astrakhan HA reported 3-fold lower neutralizing titers against A/pheasant/New York/22-009066-001/2022 that more closely matches the currently circulating H5N1 circulating in the United States27.”
From Clade 2.3.4.4b but not historical clade 1 HA replicating RNA vaccine protects against bovine H5N1 challenge in mice (2025) · cites this paper as [27]
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Avian Influenza: An Overview and Clinical Status
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Nanoparticle‐Based Antiviral Vaccines for Chickens: Recent Advances and Future Perspectives
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Deep learning-guided dual-fitness evolution of T7 RNA polymerase for enhanced stability and activity
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Preclinical evaluation of an mRNA vaccine developed from the first human isolate of bovine H5N1
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Self-citationHuman vaccination for highly pathogenic avian influenza
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Bird flu could become a human pandemic. How are countries preparing?
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A vaccine antigen central in influenza A(H5) virus antigenic space confers subtype-wide immunityPreprint
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Impfungen für neu- und wiederauftretende Viruserkrankungen
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RNA viruses: from RNA processing and interaction mechanisms to new prevention and control strategies
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Bird-flu vaccine for cattle aces early test
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Evaluation of an H5 influenza virus mRNA-lipid nanoparticle (LNP) vaccine in lactating dairy cowsPreprint
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Self-citationHow to select the best zero-shot model for the viral proteins?Preprint
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Recent Development of Cancer Vaccines
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T Cell Responses to Influenza Infections in Cattle
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Current status of H5N1 influenza vaccines against clade 2.3.4.4b of H5N1
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Immunological and virological questions for H5N1 pandemic emergence
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Epidemiological Characteristics of Influenza A Pandemic
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PEGylated Polyaspartamide Nanomicelle Delivery of Self-amplifying Avian Influenza mRNA Vaccine
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Self-citation
- Authors
- Furey, C., Scher, G., Ye, N., Kercher, L., DeBeauchamp, J., Crumpton, J. C., Jeevan, T., Patton, C., Franks, J., Rubrum, A., Alameh, M.-G., Fan, S. H. Y., Phan, A. T., Hunter, C. A., Webby, R. J., Weissman, D., & Hensley, S. E.
- Affiliations
- University of Pennsylvania (US)
- St. Jude Children's Research Hospital (US)
- Acuitas Therapeutics (Canada) (CA)
- Corresponding author
- Hensley, Scott E.
- ORCID
- Venue
- Nature Communications
- Published
- 2024-05-23
- Volume
- 15
- Issue
- 1
- Pages
- 4350-4350
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC10168367
- OpenAlex
- W4398240584
- Cited by
- 79
- References
- 40
- Citations by year
- 2026: 18 · 2025: 41 · 2024: 19 · 2023: 1
- FWCI
- 23.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Health & Human Services | National Institutes of Health (75N93021C00015, 75N93021C00016, R01AI08686, R01AI126899)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Keywords
- mRNA vaccines, lipid nanoparticles, H5N1 avian influenza, clade 2.3.4.4b, hemagglutinin, nucleoside modification, neutralizing antibodies, T cell response, pandemic influenza preparedness
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