Transmission and evolutionary dynamics of H9N2 avian influenza virus in the inactivated vaccinated chickens

H9N2 AIVs is not only endemic in poultry and wild birds worldwide, but appears increasingly zoonotic and acts as a major gene donor to emerging AIVs. Thus, control of H9N2 AIVs is of key importance to the poultry industry and to public health. Despite long-term and widespread use of inactivated whole virus vaccines in many countries, H9N2 AIVs remain dominant in vaccinated and unvaccinated chickens. We demonstrate that inactivated vaccine cannot prevent the replication of H9N2 AIVs in the upper airway of chickens regardless of vaccination status. Inactivated vaccine induced insufficient IgG at the airway lining to confer humoral protection against H9N2 virus infection. In sequential H9N2 virus transmission studies with vaccinated and immunologically naïve chickens, virus replication and transmission were enhanced in vaccinated chickens. We further show that improved H9N2 virus replication and transmission in vaccinated birds was attributed to restriction in defective interfering particles production and induction of stable mutations in NP, M and NS gene segments that promote virus replication without affecting antigenic drift. Notably, genetic diversity of H9N2 AIVs generated during infection was greater through vaccinated than naïve chickens, which included more mammalian/human adapted mutations emerging from vaccinated birds. Taken together, present inactivated H9N2 vaccine is ineffective and potentially harmful to public health, and, in the face of continued increase in replication ability of H9N2 AIVs in chickens and mammals, current vaccination practice to control H9N2 AIVs needs urgent review and change.

Zhen Wang, National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China; Zhe Hu, National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China; Yipeng Sun, National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China; Jinhua Liu, National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China

Avian influenza in mammals, pandemic preparedness, and one health