Development of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus

Colleen Furey, Gabrielle Scher, Naiqing Ye, Lisa Kercher, Jennifer DeBeauchamp, Jeri Carol Crumpton, Trushar Jeevan, Christopher Patton, John Franks, Adam Rubrum, Mohamad-Gabriel Alameh, Steven H. Y. Fan, Anthony T. Phan, Christopher A. Hunter, Richard J. Webby, Drew Weissman and Scott E. Hensley ()
Additional contact information
Colleen Furey: University of Pennsylvania
Gabrielle Scher: University of Pennsylvania
Naiqing Ye: University of Pennsylvania
Lisa Kercher: St. Jude Children’s Research Hospital
Jennifer DeBeauchamp: St. Jude Children’s Research Hospital
Jeri Carol Crumpton: St. Jude Children’s Research Hospital
Trushar Jeevan: St. Jude Children’s Research Hospital
Christopher Patton: St. Jude Children’s Research Hospital
John Franks: St. Jude Children’s Research Hospital
Adam Rubrum: St. Jude Children’s Research Hospital
Mohamad-Gabriel Alameh: University of Pennsylvania
Steven H. Y. Fan: Acuitas Therapeutics
Anthony T. Phan: University of Pennsylvania
Christopher A. Hunter: University of Pennsylvania
Richard J. Webby: St. Jude Children’s Research Hospital
Drew Weissman: University of Pennsylvania
Scott E. Hensley: University of Pennsylvania

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-48555-z

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