An influenza mRNA vaccine protects ferrets from lethal infection with highly pathogenic avian influenza A(H5N1) virus
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.
Authors
- Chenchen Feng
- Ying Huang (ORCID: https://orcid.org/0000-0002-6889-5301)
- Jana M. Ritter (ORCID: https://orcid.org/0000-0002-4768-162X)
- Juan A. De La Cruz (ORCID: https://orcid.org/0000-0002-0712-065X)
- Jaber Hossain
- Jimma Liddell (ORCID: https://orcid.org/0009-0007-0226-5183)
- John Steel (ORCID: https://orcid.org/0000-0003-1217-0990)
- Yasuko Hatta (ORCID: https://orcid.org/0009-0000-1024-3792)
- Raffael Nachbagauer (ORCID: https://orcid.org/0000-0001-5568-5420)
- Thomas Rowe (ORCID: https://orcid.org/0009-0003-0518-7118)
- Bin Zhou (ORCID: https://orcid.org/0000-0002-1535-6283)
- David E. Wentworth (ORCID: https://orcid.org/0000-0002-5190-980X)
- Elizabeth A. Pusch (ORCID: https://orcid.org/0000-0001-8193-710X)
- C. Todd Davis (ORCID: https://orcid.org/0000-0002-1429-974X)
- Angela Choi (ORCID: https://orcid.org/0000-0002-4131-2292)
- Daniel Stadlbauer (ORCID: https://orcid.org/0000-0001-6792-7650)
- Nannan Jiang (ORCID: https://orcid.org/0000-0003-3375-4805)
- Marie K. Kirby (ORCID: https://orcid.org/0000-0003-0859-9604)
- John Barnes (ORCID: https://orcid.org/0000-0002-5874-4411)
- Carole Henry (ORCID: https://orcid.org/0000-0002-5696-527X)
- Joseph R Rouse (ORCID: https://orcid.org/0000-0001-8675-904X)
- Min Z. Levine (ORCID: https://orcid.org/0000-0002-3197-1649)
- Matthew W. Keller (ORCID: https://orcid.org/0000-0002-5850-1698)
- Li Liu (ORCID: https://orcid.org/0000-0001-5830-8671)
- Li Wang (ORCID: https://orcid.org/0000-0003-3722-5986)
- Monique Johnson
- Michael Currier
- Han Di (ORCID: https://orcid.org/0009-0008-0672-1497)
- A K Bhattacharjee
- Masato Hatta (ORCID: https://orcid.org/0000-0002-5532-2942)
- Emma Fang
Institutions
- Centers for Disease Control and Prevention (US)
- National Center for Immunization and Respiratory Diseases (US)
- Moderna Therapeutics (United States) (US)
- National Center for Emerging and Zoonotic Infectious Diseases (US)
- Decatur Memorial Hospital (US)
Publication Details
- Journal
- Science Translational Medicine
- Published
- 2024-12-18
- DOI
- https://doi.org/10.1126/scitranslmed.ads1273
- Citations
- 33
- Primary Topic
- Influenza Virus Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 12.76
Funders
- U.S. Department of Health and Human Services
- Moderna
- Centers for Disease Control and Prevention