Avian influenza virus prevention in the domestic host by a deactivated vaccine

The National Institute of Allergy and Infectious Diseases awarded Thomas Jefferson University $221,250 on June 17, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop and evaluate a rabies-vectored vaccine against highly pathogenic avian influenza H5N1.

The research will compare hemagglutinin and neuraminidase-based rabies-vectored vaccines expressing H5 antigens of clade 2.3.4.4B with and without an adjuvant (SEPIVAC SWE) in mouse challenge models using both single-immunization and prime/boost approaches. The team will assess T-cell involvement through CD4/CD8 depletion studies before viral challenge. The second phase will apply the identified vaccine approach to dairy cows, evaluating efficacy against intransal and intramammary challenges and examining the role of vaccine-induced antibodies through passive transfer studies of purified IgG from vaccinated animals.

Performance occurs in Philadelphia, Pennsylvania, with a period of performance through May 31, 2028. The award is structured as a Project Grant.

Abstract

Influenza viruses, which affect both birds and mammals, pose a substantial public health concern. An estimated 10% of the global population annually becomes infected, resulting in 300,000 to 600,000 deaths worldwide. Our research objectives are to develop a hemagglutinin (HA) and neuraminidase (NA) based rabies-vectored vaccine against highly pathogenic avian influenza (hpai) a virus H5N1. We have already demonstrated the vaccine's immunogenicity and protective efficacy against hpai H5N1 vietnam 1203. To advance this research, we propose to utilize a novel ravb-based deactivated vaccine that harbors the H5 antigens of the current homologous circulation (clade 2.3.4.4B) and a construct expressing N1. Our first aim will involve comparing the H5 or H5/N1 rabv-based vaccines against challenges by PR8 recombinants carrying H5N1 proteins in mice. We will employ a single immunization and a prime/boost approach, either with or without an adjuvant approved for use in animals and humans (sepivac SWE™). We will assess the role of t cells in the vaccine-induced protection by performing CD4/CD8 depletion before challenge our second aim will utilize the vaccine approach identified to protect our mouse system in dairy cows. Subsequently, we will assess the vaccine's efficacy against challenges administered intranasally and intramammary. We will verify the role of the vaccine-induced antibodies in protection against H5N1 by performing passive transfer studies of purified IGG from vaccinated cows before challenge. In summary, this study will evaluate the efficacy and delineate the mechanism of protection of a safe and well- established vaccine platform to protect against hpai H5 and explore its potential as an animal and human vaccine.