Infectious Diseases 2025

Clade 2.3.4.4b H5 highly pathogenic avian influenza (HPAI) continues to cause devastating global losses in poultry, with turkeys being among the most vulnerable species. Turkeys require a lower infectious dose compared to chickens and often exhibit more severe disease outcomes. Despite this, data on vaccine performance in turkeys remain limited compared with chickens. A new study by Lee et al. (2025) evaluated the efficacy of an inactivated, reverse-genetics–based H5N9 vaccine against a contemporary turkey H5N1 isolate to determine its protective capacity.
Commercial broad-breasted white turkeys were vaccinated at different ages (3, 7, or 9 weeks) with a single dose of an inactivated H5N9 vaccine containing a clade 2.3.4.4b H5 hemagglutinin and a North American wild bird-derived N9 neuraminidase. At 10 weeks of age, all groups were challenged with the homologous H5N1 virus A/turkey/Indiana/22-003707-003/2022 (TK/IN/22).
Protection and survival: All vaccinated groups showed 100% survival, while sham-vaccinated controls had 0% survival.
Clinical outcomes: Only two turkeys in the 9-week group exhibited mild clinical signs, reflecting reduced time for immune response development.
Viral shedding: Vaccinated groups shed significantly less virus via both oropharyngeal and cloacal routes compared to controls. The 3-week vaccination group shed the least, while the 9-week group shed more virus, particularly cloacally.
Antibody responses: Hemagglutination inhibition (HI) titers varied depending on age at vaccination, with younger vaccination producing stronger responses. The neuraminidase inhibition enzyme-linked lectin assay (NI-ELLA) proved more sensitive than HI, detecting antibodies even when HI was negative. NI-ELLA also showed potential as a DIVA (Differentiating Infected from Vaccinated Animals) tool.
Duration of Immunity: The study by Lee et al. specifically evaluated vaccine efficacy when turkeys were challenged 7 weeks after vaccination. However, the experiment did not extend beyond this timeframe. As the authors note, protection in turkeys may begin to wane between 7 and 13 weeks post-vaccination, based on earlier studies. Therefore, while the data confirm short-term efficacy, they do not define the full duration of immunity or the optimal prime-boost schedules required to maintain flock protection throughout the entire production cycle or in long-lived birds such as breeders.
Turkeys are highly susceptible to H5N1, often becoming infected at lower viral doses and suffering higher mortality than chickens. This makes them a sentinel and high-risk species in HPAI outbreaks. Demonstrating that vaccination provides complete survival, coupled with reduced shedding, directly supports vaccination as a practical and necessary control tool to mitigate both mortality and onward transmission in commercial turkey production.
The results underscore the value of vaccination as a complementary strategy alongside biosecurity and surveillance. By reducing viral shedding and preventing clinical disease in turkeys, vaccines can lower environmental contamination, decrease spillover risk to other poultry or wildlife, and reduce the likelihood of viral adaptation events. Moreover, the ability to apply DIVA-compatible serological tools strengthens the feasibility of vaccination without compromising surveillance. These findings reinforce the case for targeted vaccination programs in turkeys as part of integrated HPAI control strategies.