Masato Hatta

National Center for Immunization and Respiratory Diseases

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Carole Henry

Moderna Therapeutics (United States)

Joseph R Rouse

Medical College of Wisconsin

John Barnes

Centers for Disease Control and Prevention

Ying Huang

University of Georgia

Li Wang

Vanderbilt University Medical Center

Matthew W. Keller

Centers for Disease Control and Prevention

Marie K. Kirby

Centers for Disease Control and Prevention

Jaber Hossain

Centers for Disease Control and Prevention

Emma Fang

National Center for Immunization and Respiratory Diseases

Thomas Rowe

Centers for Disease Control and Prevention

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Centers for Disease Control and Prevention

National Center for Immunization and Respiratory Diseases

Moderna Therapeutics (United States)

Icahn School of Medicine at Mount Sinai

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Oak Ridge Associated Universities

Oak Ridge Institute for Science and Education

National Institute of Infectious Diseases

University of Georgia

The Francis Crick Institute

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An influenza mRNA vaccine protects ferrets from lethal infection with highly pathogenic avian influenza A(H5N1) virus

Science Translational Medicine (2024)

Masato Hatta Yasuko Hatta Angela Choi Jaber Hossain Chenchen Feng

The global spread of the highly pathogenic avian influenza (HPAI) A(H5N1) virus poses a serious pandemic threat, necessitating the swift development of effective vaccines. The success of messenger RNA (mRNA) vaccine technology in the COVID-19 pandemic, marked by its rapid development and scalability, demonstrates its potential for addressing other infectious threats, such as HPAI A(H5N1). We therefore evaluated mRNA vaccine candidates targeting panzootic influenza A(H5) clade 2.3.4.4b viruses, which have been shown to infect a range of mammalian species, including most recently being detected in dairy cattle. Ferrets were immunized with mRNA vaccines encoding either hemagglutinin alone or hemagglutinin and neuraminidase, derived from a 2.3.4.4b prototype vaccine virus recommended by the World Health Organization. Kinetics of the immune responses, as well as protection against a lethal challenge dose of A(H5N1) virus, were assessed. Two doses of mRNA vaccination elicited robust neutralizing antibody titers against a 2022 avian isolate and a 2024 human isolate. Further, mRNA vaccination conferred protection from lethal challenge, whereas all unvaccinated ferrets succumbed to infection. It also reduced viral titers in the upper and lower respiratory tracts of infected ferrets. These results underscore the effectiveness of mRNA vaccines against HPAI A(H5N1), showcasing their potential as a vaccine platform for future influenza pandemics.

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10.1126/scitranslmed.ads1273

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