Optimized electroporation-mediated delivery enhances the immunogenicity of an H5/H7 trivalent avian influenza DNA vaccine

Highly pathogenic avian influenza viruses (HPAIVs) of the H5 and H7 subtypes continue to cause devastating outbreaks in poultry worldwide, resulting in substantial economic losses and persistent zoonotic threats. The H5 and H7 subtypes have demonstrated remarkable capacity for interspecies transmission, with documented spillover events from poultry to wild birds, mammals, and humans, underscoring the urgent need for effective control measures. China has adopted a vaccination-centered control strategy against HPAIVs, which has effectively prevented large-scale poultry outbreaks and reduced zoonotic human infections, achieving remarkable preventive outcomes. In March 2024, China officially approved an H5/H7 trivalent avian influenza DNA vaccine (pH5-FJ/H5-Re13, pH5-SX/H5-Re14, pH7-YN/H7-Re4), which has since been deployed for field use. DNA vaccines offer several theoretical advantages over conventional inactivated and live-attenuated vaccines, including enhanced stability, ease of manufacturing, and the capacity to encode multiple antigens simultaneously. However, naked DNA vaccines are susceptible to degradation by extracellular nucleases and exhibit poor cellular uptake, limiting their immunogenicity under field conditions.