Efficacy and Limitations of an Improved Vaccine Derived from an Updated Vaccine Strain Against H5 High Pathogenicity Avian Influenza

Although biosecurity and stamping out are key control measures, vaccination in poultry is an additional tool against H5 high pathogenicity avian influenza (HPAI) outbreaks to reduce disease risk and facilitate timely containment. This study aims to establish a candidate vaccine strain against H5 HPAI in Asia and validate its protective efficacy. Based on genetic and antigenic analyses, A/duck/Vietnam/HU16-DD3/2023 (H5N1), collected in northern Vietnam, was selected for establishing the vaccine candidate strain. The vaccine strain, rgPR8/VN23HA∆KRRK-NA (H5N1; rgPR8/VN23), was generated. Inactivated oil-adjuvanted vaccines were prepared from rgPR8/VN23 (H5N1), NIID-002 (H5N1), which originated from HPAI virus, A/Ezo red fox/Hokkaido/1/2022 (H5N1; Fox/Hok/1/22), and a Japanese stockpiled vaccine strain with a distinct antigen. These vaccines were intramuscularly injected into juvenile chickens or adult laying hens. All vaccinated juvenile chickens acquired optimal immunity and survived for 14 days after intranasal challenge with Fox/Hok/1/22 at 21 days post-vaccination (dpv). The rgPR8/VN23 and NIID-002 vaccines markedly reduced virus shedding, suggesting near-sterile protection. However, low-titer viruses were transiently detected in chickens vaccinated with the stockpiled vaccine strain. The rgPR8/VN23 vaccine induced immunity in juvenile chickens against Fox/Hok/1/22 as early as 8 dpv. Intriguingly, a single dose of vaccine was insufficient to provide protective immunity to laying hens. Protective efficacy increased with a double-volume dose vaccine. These data confirm that the antigenicity-matched vaccine conferred sterilized immunity in 21 days and clinical protection in 8 days to juvenile chickens, although complete protection of hens may require a refined vaccination strategy.