Intranasal deliverable mannose surface conjugated chitosan-based influenza nanovaccine for nursery pigs

Research poster
Sankar Renu
Post Doctoral
Renukaradhya Gourapura
Food Animal Health Research Program

Virulent swine influenza A virus (SwIAV) infection causes acute febrile respiratory disease in pigs of all ages. The triple reassortant 2009 pandemic SwIAV-H1N1 spillover to humans is evidence that pig can act as a mixing vessel for mammalian and avian influenza viruses. The commercial inactivated SwIAV vaccine is a multivalent formulation administered by intramuscular (IM) injection. It induces systemic IgG with poor induction of mucosal secretory IgA (SIgA) antibody response. SIgA antibody is important because SwIAV enters the body through airways and replicates primarily in the respiratory tract epithelial cells. Therefore, intranasal (IN) vaccination is the ideal approach to mimic the natural virus infection-induced mucosal immunity. However, IN delivered antigens are poorly immunogenic, and they need a suitable adjuvant and vaccine delivery system to trigger mucosal immune response. Thus, we conjugated a ligand mannose on natural mucoadhesive chitosan nanoparticles (CS NPs), which helps in recognizing and uptake of particle antigens by dendritic cells. IN delivery of killed/inactivated SwIAV antigen (KAg) loaded mannose-conjugated CS NPs (mCS NPs-KAg) in pigs was shown to be internalized by mucosal immune cells in nasal turbinate and lymph nodes germinal center compared to unmodified CS NPs. Similarly, in vitro treated pig immune cells with mCS NPs-KAg was found internalized. Maternally derived antibodies carrying nursery pigs vaccinated IN with mCS NPs-KAg induced significantly increased SIgA antibodies and reduced heterologous challenge virus load compared to commercial vaccine. In conclusion, mannose modified influenza nanovaccine delivered IN in pig targets immune cells and elicits antibody response which mediates cross-protection.