Polyanhydride nanovaccine against swine influenza virus in pigs

Abstract

We have recently demonstrated the effectiveness of an influenza A virus (IAV) subunit vaccine based onbiodegradable polyanhydride nanoparticles delivery in mice. In the present study, we evaluated the effi-cacy of 200 nm polyanhydride nanoparticles encapsulating inactivated swine influenza A virus (SwIAV)as a vaccine to induce protective immunity against a heterologous IAV challenge in pigs. Nursery pigswere vaccinated intranasally twice with inactivated SwIAV H1N2 (KAg) or polyanhydride nanoparticle-encapsulated KAg (KAg nanovaccine), and efficacy was evaluated against a heterologous zoonotic virulentSwIAV H1N1 challenge. Pigs were monitored for fever daily. Local and systemic antibody responses,antigen-specific proliferation of peripheral blood mononuclear cells, gross and microscopic lung lesions,and virus load in the respiratory tract were compared among the groups of animals. Our pre-challengeresults indicated that KAg nanovaccine induced virus-specific lymphocyte proliferation and increasedthe frequency of CD4+CD8aa+T helper and CD8+cytotoxic T cells in peripheral blood mononuclear cells.KAg nanovaccine-immunized pigs were protected from fever following SwIAV challenge. In addition, pigsimmunized with the KAg nanovaccine presented with lower viral antigens in lung sections and had 6 to8-fold reduction in nasal shedding of SwIAV four days post-challenge compared to control animals.Immunologically, increased IFN-csecreting T lymphocyte populations against both the vaccine and chal-lenge viruses were detected in KAg nanovaccine-immunized pigs compared to the animals immunizedwith KAg alone. However, in the KAg nanovaccine-immunized pigs, hemagglutination inhibition, IgGand IgA antibody responses, and virus neutralization titers were comparable to that in the animals immu-nized with KAg alone. Overall, our data indicated that intranasal delivery of polyanhydride-based SwIAVnanovaccine augmented antigen-specific cellular immune response in pigs, with promise to induce cross-protective immunity