Evaluation of CpG-ODN-adjuvanted polyanhydride-based intranasal influenza nanovaccine in pigs

Influenza results in significant economic loss in the swine industry each year. A broadly protective swine influenza vaccine would have the dual benefit of protecting pigs from influenza A viruses (IAVs) and limiting their possible zoonotic transmission to humans. In this study, we developed polyanhydride nanoparticles-based swine influenza vaccine (KAg + CpG-nanovaccine) co-encapsulating inacticated/killed soluble antigen (KAg) and Toll like receptor (TLR)-9 agonist (CpG-ODN). The immunogenicity and protective efficacy of KAg + CpG-nanovaccine was compared with KAg vaccine containing five-times greater quantity of antigens following heterologous virus challenge. Prime-boost intranasally delivered KAg + CpG-nanovaccine induced significantly higher levels of cross-reactive antigen-specific IgA antibody responses in the nasal cavity, greater lymphoproliferative response in peripheral blood mononuclear cells (PBMCs), and higher IFN-y secretion during antigen -induced recall responses of PBMCs and tracheobronchial lymph nodes cells compared to those immunized with KAg alone. Importantly, KAg + CpG-nanovaccine provided better protective efficacy through a significant reduction in influenza-induced fever, 16-fold reduction of nasal virus shedding and 80-fold reduction in lung virus titers compared to those immunized with soluble KAg. Our results indicated that CpG-ODN-adjuvanted polyanhydride nanovaccine can induce higher mucosal antibody and cellular immune responses in pigs; and provide better protection as compared with intranasally delivered soluble KAg.