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DNA vaccine-encapsulated virus-like particles derived from an orally transmissible virus stimulate mucosal and systemic immune responses by oral administration

Gene Therapy volume 11, pages 628–635 (2004)Cite this article

Abstract

Delivery of foreign genes to the digestive tract mucosa by oral administration of nonreplicating gene transfer vectors would be a very useful method for vaccination and gene therapy. However, there have been few reports on suitable vectors. In the present study, we found that plasmid DNA can be packaged in vitro into a virus-like particle (VLP) composed of open reading frame 2 of hepatitis E virus, which is an orally transmissible virus, and that these VLPs can deliver this foreign DNA to the intestinal mucosa in vivo. The delivery of plasmid DNA to the mucosa of the small intestine was confirmed by the results of immunohistochemical analyses using an expression plasmid encoding human immunodeficiency virus env (HIV env) gp120. After oral administration of VLPs loaded with HIV env cDNA, significant levels of specific IgG and IgA to HIV env in fecal extracts and sera were found. Moreover, mice used in this study exhibited cytotoxic T-lymphocyte responses specific to HIV env in the spleen, Payer's patches and mesenteric lymph nodes. These findings suggest that VLPs derived from orally transmissible viruses can be used as vectors for delivery of genes to mucosal tissue by oral administration for the purpose of DNA vaccination and gene therapy.

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Acknowledgements

This work was supported by Health Science Research Grants from the Ministry of Health, Labor and Welfare of Japan and the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Department of Bioregulation, Mie University School of Medicine, Mie, Japan

    S Takamura & Y Yasutomi

  2. Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan

    M Niikura

  3. Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan

    T-C Li, N Takeda & T Miyamura

  4. Laboratory of Molecular Virology and Epidemiology, AIDS Research Center, National Institute of Infectious Disease, Tokyo, Japan

    S Kusagawa & Y Takebe

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  1. S Takamura
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Takamura, S., Niikura, M., Li, TC. et al. DNA vaccine-encapsulated virus-like particles derived from an orally transmissible virus stimulate mucosal and systemic immune responses by oral administration. Gene Ther 11, 628–635 (2004). https://doi.org/10.1038/sj.gt.3302193

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