National Institute of Animal Health (NIAH)

Topics in Animal Health Research 2014

18. Development of a vaccine against highly pathogenic avian influenza virus by attenuation using reverse genetics


A vaccine for highly pathogenic avian influenza viruses (HPAIVs) was produced using attenuated H5 subtype vaccine strains generated by reverse genetics. This method enables the use of H5 subtype viruses possessing the same antigenicity of H5 subtype HPAIVs, in a biosafety level 2 facility. The recombinant vaccine strain was stable genetically by the 5th passage in embryonated eggs. The strain contained the haemagglutinin (HA) gene from the H5N1 subtype HPAIV attenuated by genetic modification at the cleavage site and the neuraminidase (NA) gene derived from the H5N1 subtype HPAI or the H5N3 subtype of avian influenza virus. The vaccinated chickens could be distinguished from unvaccinated, infected chickens by detection of N3 antibody in chickens vaccinated with H5N3 subtype strain, after challenge with H5N1 subtype HPAIV. There were no differences in HI (haemagglutinin inhibition) titre, the survival rate of chickens, and the titre of shed virus, upon vaccination with either H5N1 or H5N3 strains followed by viral challenge. Vaccination with 5 times higher dose of antigen than the normal dose was effective in increasing survival and efficiently reduced viral shedding even on challenge with a virus of a different HA clade. This study demonstrated that the use of reverse genetics would be an option for prompt production of an inactivated vaccine with better matching of antigenicity to a circulating strain.
(Influenza and Prion Research Center)


Uchida Y. et al (2014) J. Vet. Med. Sci. 76(8):1111-1117