Protective HPAI H5N1 mucosal vaccine

We developed attenuated Bovine Parainfluenza Virus type 3 genotype C (BPI3Vc) vaccine vector that induces mucosal and systemic immunity. Prototype vaccines expressing protective antigens from BPI3V or Bovine Viral Diarrhea Virus (BVDV) elicited strong, broadly neutralizing antibody responses in cattle and conferred protection against diverse BPI3V and BVDV strains. These findings validate the BPI3Vc platform as a versatile vaccine vector with broad potential for preventing respiratory diseases in cattle (Sang, H. et al. 2026. PMCID: PMC12947274; and PMCID: PMC13223107).

We used the BPI3Vc vector to generate virus expressing Highly Pathogenic Avian Influenza Virus (HPAI) H5N1 antigens, including hemagglutinin, neuraminidase, and M2e on the surface of infected cells, and nucleoprotein intracellularly. This design is intended to stimulate both humoral and cellular immunity by eliciting neutralizing antibodies and virus-specific T-cell responses. In a preliminary study, a two-dose mucosal immunization regimen with the prototype BPI3Vc-H5N1 vaccine, was safe and elicited robust HA-specific antibody responses in dry cows and provided complete protection against intramammary HPAI H5N1 challenge. In contrast, all negative controls developed disease and exhibited high viral loads following challenge. Immunization of piglets using the same regimen, similarly primed antibody responses that were robustly recalled following boosting.

Interestingly, the BPI3Vc-H5N1 vaccine expresses the H5N1 antigens efficiently in primary chicken embryo fibroblasts, highlighting the platform's potential as a vaccine for cattle, swine, and poultry. Studies are underway to test the BPI3Vc-H5N1 vaccine following in ovo administration to embryonated eggs, as well as spray vaccination of day-old chicks and pullets. In parallel, we are developing a lateral flow device to enable Differentiation of Infected from Vaccinated Animals, facilitating disease surveillance and vaccine deployment.