Induction of cross-protection against influenza A virus by DNA prime-intranasal protein boost strategy based on nucleoprotein

The highly conserved nucleoprotein (NP) is an internal protein of influenza virus and is capable of inducing cross-protective immunity against different influenza A viruses, making it a main target of universal influenza vaccine. In current study, we characterized the immune response induced by DNA prime-intranasal protein boost strategy based on NP (A/PR/8/34, H1N1) in mouse model, and evaluated its protection ability against a lethal dose challenge of influenza virus. The intranasal boost with recombinant NP (rNP) protein could effectively enhance the pre-immune response induced by the NP DNA vaccine in mice. Compared to the vaccination with NP DNA or rNP protein alone, the prime-boost strategy increased the level of NP specific serum antibody, enhanced the T cell immune response, and relatively induced more mucosal IgA antibody. The overall immune response induced by this heterologous prime-boost regimen was Th-1-biased. Furthermore, the immune response in mice induced by this strategy provided not only protection against the homologous virus but also cross-protection against a heterosubtypic H9N2 strain. The NP DNA prime-intranasal protein boost strategy may provide an effective strategy for universal influenza vaccine development.