title: Induction of cross-protection against influenza A virus by DNA prime-intranasal protein boost strategy based on nucleoprotein.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  The NP DNA prime-intranasal protein boost strategy may provide an effective strategy for universal influenza vaccine development.
authors.affiliation: Shanghai Institute of Biological Products, Shanghai 200052, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Luo
authors.forename: Dan
authors.initials: D
authors.lastname: Zheng
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.forename: Hanzhong
authors.initials: H
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Yahong
authors.initials: Y
authors.lastname: Ding
authors.forename: Chengfei
authors.initials: C
authors.lastname: Xu
authors.forename: Quanjiao
authors.initials: Q
authors.lastname: Chen
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhang
authors.forename: Ding
authors.initials: D
authors.lastname: Huang
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
authors.forename: Ze
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D056738:Cross Protection / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007114:Immunization; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053127:Influenza A Virus, H9N2 Subtype / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D019251:Nucleocapsid / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000401:mortality / Q000517:prevention & control*; D020545:Respiratory Mucosa / Q000276:immunology; D019444:Vaccines, DNA
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D019444:Vaccines, DNA