Biodegradable Nanoparticle Delivery of Inactivated Swine Influenza Virus Vaccine Provides Heterologous Cell-Mediated Immune Response in Pigs

Swine influenza virus (SwIV) causes considerable economic loss to pig industry, and some SwIV are zoonotic. This study was conducted to evaluate the cross-protective efficacy of PLGA (poly lactic-co-glycolic acid) nanoparticles (NPs) encapsulated SwIV vaccine in pigs. Killed SwIV H1N2 (δ lineage) antigens (KAg) were encapsulated in PLGA NPs of 200–300 nm (PLGA-KAg NPs), and influenza antibody-free pigs were prime-boost vaccinated intranasally as mist and challenged using a heterologous, virulent and zoonotic SwIV H1N1 (γ lineage). PLGA-KAg NPs induced maturation of pig macrophages and dendritic cells in vitro. In vaccinated pigs, PLGA-KAg NPs induced antigen specific lymphocyte proliferation and enhanced the frequency of T-helper/memory cells and cytotoxic T cells in peripheral blood mononuclear cells (PBMCs). In virus challenged pigs, the PLGA-KAg NPs vaccine rescued virus induced clinical fever, reduced the gross lung pathology, reduced the virus load in the lung sections with complete clearance of the virus from the lungs of most of the pigs; but the nasal virus shedding was not reduced. Immunologically, at post-challenge day 6 in a recall response in PBMCs of PLGA KAg NPs vaccinated pigs, a significant increase in IFN-γ secreting T cells against both vaccine and challenge viruses were detected. However, humoral immune response in those pigs was not augmented. In conclusion, intranasal delivery of PLGA NPs based SwIV induced cross-protective response through specific cell-mediated response. Future studies are aimed at boosting the mucosal antibody response.