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

Virol J. 2012 Nov 23:9:286. doi: 10.1186/1743-422X-9-286.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Cross Protection / immunology*
  • Disease Models, Animal
  • Female
  • Humans
  • Immunity, Cellular
  • Immunization
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H9N2 Subtype / immunology
  • Influenza A virus / immunology*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Mice
  • Nucleocapsid / immunology*
  • Orthomyxoviridae Infections / mortality
  • Orthomyxoviridae Infections / prevention & control*
  • Respiratory Mucosa / immunology
  • Vaccines, DNA*

Substances

  • Antibodies, Viral
  • Influenza Vaccines
  • Vaccines, DNA