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Cross-protection against influenza virus infection by intranasal administration of M2-based vaccine with chitosan as an adjuvant

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Abstract

Influenza vaccines based on conserved antigens could provide cross-protection against infections by multiple subtypes of influenza A virus. Influenza matrix protein 2 (M2) is highly conserved in all influenza A strains. In this study, we deleted the transmembrane domain of the M2 of the avian influenza virus (AIV) A/Chicken/Jiangsu/7/2002 (H9N2) strain to create an M2 without a transmembrane domain, named sM2, which was efficiently expressed in Escherichia coli. The sM2 protein was administered intranasally to mice in combination with chitosan adjuvant three times at an interval of 3 weeks. Three weeks after the last immunization, the mice were challenged with a lethal dose (5 × LD50) of A/Chicken/Jiangsu/7/2002 (H9N2) virus, PR8 (H1N1) virus and A/Chicken/Henan/12/2004 (H5N1) virus. The protective immunity of the vaccine was evaluated by determining the survival rates, residual lung virus titers, body weight, and the serum antibody titers of the mice. Nasal administration of 15 μg sM2 in combination with chitosan completely protected mice against the homologous virus and protected 90 and 30% of the mice against the heterologous H1N1 and H5N1 viruses, respectively. The study indicated that the sM2 protein was a candidate antigen for a broad-spectrum influenza virus vaccine and that the adjuvant chitosan improved the efficacy of the sM2 vaccine.

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Acknowledgments

This study was supported by the following research funds: the European Union project (SP5B-CT-2006-044161); the National 973 Project (2005CB523007, 2006CB933102); the Chinese Academy of Sciences (KSCX1-YW-R-14); the National Key Technology R&D Program of China (2006BAD06A03).

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Authors and Affiliations

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

    Zhiwei Sui, Quanjiao Chen, Rui Wu, Hongbo Zhang, Hanzhong Wang & Ze Chen

  2. College of Life Sciences, Hunan Normal University, Changsha, 410081, Hunan, China

    Ze Chen

  3. Shanghai Institute of Biological Products, Shanghai, 200052, China

    Mei Zheng & Ze Chen

  4. Graduate University of Chinese Academy of Sciences, Beijing, 100049, China

    Zhiwei Sui

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  1. Zhiwei Sui
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  2. Quanjiao Chen
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  4. Hongbo Zhang
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Correspondence to Ze Chen.

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Sui, Z., Chen, Q., Wu, R. et al. Cross-protection against influenza virus infection by intranasal administration of M2-based vaccine with chitosan as an adjuvant. Arch Virol 155, 535–544 (2010). https://doi.org/10.1007/s00705-010-0621-4

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  • DOI: https://doi.org/10.1007/s00705-010-0621-4

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