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Updated: Jun 4, 2025
Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
An influenza mRNA vaccine protects ferrets from lethal infection with highly pathogenic avian influenza A(H5N1) virus
Masato Hatta1, Yasuko Hatta1, Angela Choi2
1Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
Abstract:
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.
Insights
Messenger RNA (mRNA) vaccines show promise against highly pathogenic avian influenza (HPAI) A(H5N1) virus. Studies demonstrate mRNA vaccine candidates provide protection against HPAI A(H5N1) in ferrets, reducing viral load and preventing lethal outcomes.
Area of Science:
- Virology
- Vaccinology
- Immunology
Background:
- Highly pathogenic avian influenza (HPAI) A(H5N1) poses a significant pandemic risk.
- Messenger RNA (mRNA) vaccine technology offers rapid development and scalability for emerging infectious diseases.
- Recent HPAI A(H5N1) clade 2.3.4.4b outbreaks in mammals, including cattle, highlight the urgent need for effective vaccines.
Purpose of the Study:
- To evaluate the efficacy of mRNA vaccine candidates against panzootic HPAI A(H5N1) clade 2.3.4.4b viruses.
- To assess the immunogenicity and protective potential of mRNA vaccines encoding hemagglutinin (HA) or HA and neuraminidase (NA).
Main Methods:
- Ferrets were immunized with two doses of mRNA vaccines encoding HA or HA and NA from a WHO-recommended prototype virus.
- Immune responses, including neutralizing antibody titers, were measured.
- Protection against a lethal challenge dose of A(H5N1) virus was assessed, along with viral titers in respiratory tracts.
Main Results:
- mRNA vaccination elicited robust neutralizing antibody titers against contemporary avian and human HPAI A(H5N1) isolates.
- Vaccinated ferrets demonstrated significant protection against lethal A(H5N1) challenge, with unvaccinated controls succumbing to infection.
- Reduced viral loads were observed in the upper and lower respiratory tracts of vaccinated, infected ferrets.
Conclusions:
- mRNA vaccines are effective against highly pathogenic avian influenza A(H5N1).
- The mRNA platform demonstrates potential for rapid development and deployment against HPAI A(H5N1) and future influenza pandemics.
