Evaluation of Commercial Vaccines for Efficacy and Transmission Control Against the Emergent H5N8 (Clade 2.3.4.4b) Avian Influenza Virus in Kazakhstan

Introduction: Highly pathogenic avian influenza H5N8 (clade 2.3.4.4b) has caused devastating poultry outbreaks globally, including in Kazakhstan, underscoring the need for vaccines that protect birds and curb virus transmission. We evaluated the efficacy of three commercial H5 vaccines and an experimental homologous H5N8 vaccine in chickens. Methods: Chickens received a single dose of each vaccine, and antibody titers were measured over 4 weeks. At 30 days post-vaccination, birds were challenged intranasally with a virulent H5N8 strain and monitored for 10 days for survival and clinical signs. Virus titers in tracheal and cloacal swabs (days 1, 3, 5 post-challenge) measured shedding, and unvaccinated sentinel chickens were co-housed to assess transmission. Results: The homologous H5N8 vaccine and a closely related commercial vaccine elicited rapid, high antibody responses and conferred 100% survival. In contrast, two antigenically mismatched vaccines induced slower, lower immunity, resulting in 40-60% mortality and high virus shedding after challenge. Only the homologous vaccine sharply reduced viral shedding and significantly decreased transmission to contacts (protecting 2 of 3 sentinel birds), whereas the other vaccines failed to prevent transmission. Conclusion: An antigenically matched H5N8 vaccine with a potent adjuvant provided near-sterilizing immunity, preventing disease and significantly limiting viral shedding and transmission. These findings highlight the importance of using strain-matched vaccines in HPAI control strategies to avoid silent viral spread in vaccinated flocks.