Corn based nanoparticle delivered inactivated influenza virus vaccine intranasally augments mucosal immune response in pigs

Abstract

Abstract Swine influenza A virus (SwIV) causes respiratory tract infection in pigs. Available SwIV vaccines fail to provide cross-protective immunity in pigs. Nano-11 is an amphiphilic nanoparticle (70–80nm) obtained from sweet corn-derived phytoglycogen. Nano-11 carries high surface positive charge and thus facilitates easy preparation of nanoparticle based vaccine by electrostatic interaction with killed SwIAV antigen (KAg) or peptides (negative charge). Earlier we showed that Nano-11 bound killed SwIV H1N2 Ag (Nano-11+KAg) delivered intranasally in pigs induced mucosal antibody response, but the challenge heterologous H1N1 SwIV load was not substantially reduced in the airways. In this study, KAg or conserved ten IAV peptides co-adsorbed with adjuvant Poly(I:C) (negative charge) on Nano-11 [Nano-11+KAg/peptides+Poly(I:C)] was vaccinated to influenza-free pigs intranasally, twice, and challenged with a heterologous SwIV. We observed increased SIgA and IgG responses in the airways and enhanced proliferation of IFN-g+ gd T cells in PBMCs in Nano-11+KAg+Poly(I:C) vaccinates compared to control. In Nano-11+peptides+Poly(I:C) vaccinates noticed an increased proliferation of IFN-g+ gd T cells and IFN-g+ cytotoxic T cells in PBMCs compared to control. Commercial vaccine group induced higher IgG response in serum and proliferation of IFN-g+ T-helper/memory cells in PBMCs compared to control. However, reduction in challenge virus load in any of the vaccinated groups was not statistically significant. In conclusion, inclusion of Poly(I:C) in Nano-11 flu vaccine improved the T cell response, but further improvements in the vaccine formulation is required to take advantage of this easy to prepare particle based mucosal flu vaccine.