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

Jian Luo2, Dan Zheng2, Wenjie Zhang4*, Fang Fang1, Hanzhong Wang3, Ying Sun2, Yahong Ding2, Chengfei Xu2, Quanjiao Chen3, Hongbo Zhang3, Ding Huang5, Bing Sun6 and Ze Chen123*

Author Affiliations

1 College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China

2 Shanghai Institute of Biological Products, Shanghai 200052, China

3 State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China

4 Xinhua Hospital affiliated to Shanghai Jiaotong University of Medicine, Shanghai 200092, China

5 State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China

6 Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China

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Virology Journal 2012, 9:286  doi:10.1186/1743-422X-9-286

Published: 23 November 2012

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.

Keywords:
Influenza; Recombinant NP; DNA prime; Intranasal protein boost