A single-dose intramuscular immunization of pigs with lipid-nanoparticle DNA vaccines based on the hemagglutinin antigen confers complete protection against challenge infection with the homologous influenza virus strain

Influenza A virus of swine (IAV-S) is highly prevalent and causes significant economic losses to swine producers. Due to the highly variable and rapidly evolving nature of the virus, it is critical to develop a safe and versatile vaccine platform that allows frequent updates of the vaccine immunogens to cope with the emergence of new viral strains. The main objective of this study was to assess the feasibility of using lipid nanoparticles (LNPs) as a nanocarrier to deliver DNA plasmid encoding the viral hemagglutinin (HA) gene in pigs. Intramuscular administration of a single dose of the LNP-DNA vaccines resulted in robust systemic and mucosal in pigs. Importantly, the vaccinated pigs were fully protected against challenge infection with the homologous IAV-S strain, with only one out of 12 vaccinated pigs shedding a low amount of viral genomic RNA in its nasal cavity. No gross or microscopic lesions were observed in the lungs of the vaccinated pigs at necropsy. Thus, the LNP-DNA vaccines are highly effective in protecting pigs against the homologous IAV-S strain and can serve as a promising platform for the rapid development of IAV-S vaccines. Importance Influenza A virus of swine (IAV-S) is a significant pathogen of swine. The virus also poses a great public health concern due to its zoonotic potential. Although whole-inactivated virus (WIV) vaccines are available to control IAV-S, their heterologous efficacy is limited due to the substantial genetic/antigenic variation of the viral genome. This study provides compelling evidence demonstrating that lipid nanoparticle encapsulated DNA (LNP-DNA) vaccines induce robust systemic and mucosal immunity and complete protection of pigs against challenge infection with the homologous IAV-S strain. Importantly, the LNP-DNA vaccine approach meets the regulatory requirements to serve as an adaptable platform that can be frequently updated to match the emergence of new IAV-S variants. Thus, this LNP-DNA vaccine strategy exhibits great potential in effectively mitigating the economic impact of IAV-S on the swine industry and the associated public health threat.