Comparative immunogenicity and cross-protection of wild-type and reverse genetics H5N8 (clade 2.3.4.4b) oil-adjuvanted vaccines against circulating H5N1 avian influenza viruses from clades 2.3.4.4b an

Highly pathogenic avian influenza (HPAI) H5N8 viruses of clade 2.3.4.4b continue to cause devastating outbreaks worldwide, necessitating effective vaccination strategies. The comparative efficacy of wild-type versus reverse genetics (RG)-based vaccine platforms against emerging H5Nx variants remains poorly characterized, particularly regarding cross-protective immunity mechanisms. We conducted a comprehensive comparative analysis of wild-type and RG-based H5N8 (clade 2.3.4.4b) oil-adjuvanted vaccines in specific-pathogen-free chickens (n?=?150, power analysis based on detecting two-fold titre differences with 80% power, α?=?0.05). Following single-dose vaccination, we assessed humoral and cellular immune responses, protection against homologous H5N8 (clade 2.3.4.4b), antigenically drifted and heterologous challenges [H5N1 clade 2.3.4.4b and H5N1 clade 2.2.1.2], and viral shedding dynamics using standardized assays. Both vaccines induced robust homologous antibody responses (HI titres: wild-type 7.2 ± 0.15 vs. RG 6.8 ± 0.13 log2, P?3.0 log10 reduction in respiratory tissues, with strong correlation between HI titres and protection (r?=?0.89, P?