M2e nanovaccines supplemented with recombinant hemagglutinin protect chickens against heterologous HPAI H5N1 challenge

• Published in: npj vaccines Vol. 9; no. 1; pp. 161 - 13
• Main Authors: Calzas, Cynthia, Alkie, Tamiru N., Suderman, Matthew, Embury-Hyatt, Carissa, Khatri, Vinay, Le Goffic, Ronan, Berhane, Yohannes, Bourgault, Steve, Archambault, Denis, Chevalier, Christophe
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.09.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/326/590; 631/326/596; Avian flu; Biomedical and Life Sciences; Biomedicine; Chickens; Infectious Diseases; Medical Microbiology; Public Health; Vaccine; Vaccines; Virology; Viruses
• ISSN: 2059-0105; 2059-0105
• DOI: 10.1038/s41541-024-00944-7

Current poultry vaccines against influenza A viruses target the globular head region of the hemagglutinin (HA1), providing limited protection against antigenically divergent strains. Experimental subunit vaccines based on the conserved ectodomain of the matrix protein 2 (M2e) induce cross-reactive antibody responses, but fail to fully prevent virus shedding after low pathogenic avian influenza (LPAI) virus challenge, and are ineffective against highly pathogenic avian influenza (HPAI) viruses. This study assessed the benefits of combining nanoparticles bearing three tandem M2e repeats (NR-3M2e nanorings or NF-3M2e nanofilaments) with an HA1 subunit vaccine in protecting chickens against a heterologous HPAI H5N1 virus challenge. Chickens vaccinated with the combined formulations developed M2e and HA1-specific antibodies, were fully protected from clinical disease and mortality, and showed no histopathological lesions or virus shedding, unlike those given only HA1, NR-3M2e, or NF-3M2e. Thus, the combined vaccine formulations provided complete cross-protection against HPAI H5N1 virus, and prevented environmental virus shedding, crucial for controlling avian influenza outbreaks.