Effect of inactivated vaccine on H9N2 transmission and evolution in chickens
H9N2 avian influenza virus (AIV) is a low-pathogenicity virus endemic in poultry populations across Asia, the Middle East, and parts of Africa, with sporadic detection in the Americas and Europe. Despite its relatively mild clinical presentation in chickens, H9N2 AIV has significant economic consequences due to decreased productivity and increased susceptibility to secondary infections. Moreover, the virus possesses zoonotic potential, with documented transmission to mammals, including humans. Its internal gene segments have contributed to the emergence of several human-infecting avian influenza viruses (e.g., H5N6, H7N9).
A recent study published in Nature investigates the effects of inactivated H9N2 vaccines on viral replication, transmission, genetic evolution, and cross-species adaptation potential, using both in vivo transmission models and deep sequencing approaches. It also evaluates alternative vaccination strategies capable of inducing broader immune responses.
Despite widespread immunization efforts using inactivated vaccines, H9N2 AIV continues to circulate in poultry flocks and poses an increasing zoonotic threat. This study demonstrates that inactivated vaccines do not prevent H9N2 replication in the upper respiratory tract of chickens, thereby enabling virus shedding and transmission among vaccinated birds. Serial passage of the virus in vaccinated hosts led to enhanced viral replication and shortened transmission intervals, accompanied by reduced production of defective interfering particles (DIPs) and the selection of key mutations (NP-N417D, M1-V219I, NS1-R140W) that increase viral fitness.
Deep sequencing revealed greater genetic diversity and a higher number of mammalian-adaptive mutations in viruses derived from vaccinated chickens compared to those from naïve birds. Furthermore, a narrower transmission bottleneck was observed in vaccinated groups, facilitating the fixation of adaptive mutations. Live vector vaccines (rHVT-H9) and cold-adapted live attenuated vaccines (H9N2-LAIV), which elicit cellular and mucosal immunity, were significantly more effective at limiting viral replication and transmission than inactivated vaccines.
These findings highlight the critical limitations of inactivated H9N2 vaccines, particularly their role in promoting viral evolution under immune pressure. The data underscore the urgent need to revise vaccination strategies by incorporating vaccines that stimulate both systemic and mucosal immune responses to effectively control H9N2 AIV and mitigate its zoonotic potential.
