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

Colleen Furey, Naiqing Ye, Lisa Kercher, Jennifer DeBeauchamp, Jeri Carol Crumpton, Trushar Jeevan, Christopher Patton, John Franks, Mohamad-Gabriel Alameh, Steven H.Y. Fan, Anthony T. Phan, Christopher A. Hunter, Richard J. Webby, Drew Weissman, View ORCID ProfileScott E. Hensley
doi: https://doi.org/10.1101/2023.04.30.538854
Colleen Furey
1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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Naiqing Ye
1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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Lisa Kercher
2Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN, USA
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Jennifer DeBeauchamp
2Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN, USA
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Jeri Carol Crumpton
2Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN, USA
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Trushar Jeevan
2Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN, USA
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Christopher Patton
2Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN, USA
3Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38105, USA
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John Franks
2Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN, USA
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Mohamad-Gabriel Alameh
4Infectious Disease Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
5Penn Institute for RNA Innovation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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Steven H.Y. Fan
6Acuitas Therapeutics, Vancouver, BC, CAN
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Anthony T. Phan
7Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA
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Christopher A. Hunter
7Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA
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Richard J. Webby
2Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN, USA
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Drew Weissman
4Infectious Disease Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
5Penn Institute for RNA Innovation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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Scott E. Hensley
1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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  • ORCID record for Scott E. Hensley
  • For correspondence: hensley@pennmedicine.upenn.edu
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Abstract

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. We generated an mRNA lipid nanoparticle (LNP) vaccine encoding the hemagglutinin (HA) glycoprotein from a clade 2.3.4.4b H5 isolate. We show that the vaccine is immunogenic in mice and ferrets and prevents morbidity and mortality of ferrets following 2.3.4.4b H5N1 challenge.

Competing Interest Statement

S.E.H. and D.W. are co-inventors on patents that describe the use of nucleoside-modified mRNA as a platform to deliver therapeutic proteins and as a vaccine platform. S.H.Y.F. is an employee of Acuitas Therapeutics, a company focused on the development of lipid nanoparticulate nucleic acid delivery systems for therapeutic applications. The authors declare no other competing interests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 30, 2023.
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Development of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus
Colleen Furey, Naiqing Ye, Lisa Kercher, Jennifer DeBeauchamp, Jeri Carol Crumpton, Trushar Jeevan, Christopher Patton, John Franks, Mohamad-Gabriel Alameh, Steven H.Y. Fan, Anthony T. Phan, Christopher A. Hunter, Richard J. Webby, Drew Weissman, Scott E. Hensley
bioRxiv 2023.04.30.538854; doi: https://doi.org/10.1101/2023.04.30.538854
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Development of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus
Colleen Furey, Naiqing Ye, Lisa Kercher, Jennifer DeBeauchamp, Jeri Carol Crumpton, Trushar Jeevan, Christopher Patton, John Franks, Mohamad-Gabriel Alameh, Steven H.Y. Fan, Anthony T. Phan, Christopher A. Hunter, Richard J. Webby, Drew Weissman, Scott E. Hensley
bioRxiv 2023.04.30.538854; doi: https://doi.org/10.1101/2023.04.30.538854

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