Mucosal immunity and protective efficacy of inactivated influenza virus vaccine is improved by intranasal chitosan nanoparticle delivery in pigs

Abstract

Abstract Currently used inactivated influenza virus vaccines administered by intramuscular injection provide homologous protection, but the much required heterologous protection against constantly evolving field viruses is limited, attributed to lack of induction of mucosal IgA and cellular immune responses in the respiratory tract. We developed a novel vaccine delivery platform by encapsulating swine influenza A virus (SwIAV) killed/inactivated antigen (KAg) in mucoadhesive, biodegradable, polycationic chitosan nanoparticles (CNPs-KAg). The CNPs-KAg vaccine (<500nm in size) was administered through intranasal route as mist to nursery pigs twice and challenged with a zoonotic and virulent heterologous SwIAV. Pigs vaccinated with CNPs-KAg had enhanced mucosal IgA response throughout the respiratory tract against homologous (H1N2), heterologous (H1N1) and heterosubtypic (H3N2) SwIAV. In addition, the frequency of cytotoxic T cells and T helper/memory cells were increased in CNPs-KAg vaccinated pigs, together with increased level of systemic and mucosal recall IFNγ response. In heterologous virus challenged pigs, CNPs-KAg vaccine reduced the pneumonic lesions and virus titers in lungs and significantly reduced the nasal viral shedding. In conclusion, intranasal delivery of chitosan nanovaccine elicited better cross-protective mucosal IgA and cellular immune responses in the respiratory tract and reduced viral load and shedding, indicating that chitosan based influenza nanovaccine might be an ideal candidate vaccine against SwIAV infections under field conditions.