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上传于：2015-10-30

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    188宝金博页面版: CD226 as a genetic adjuvant to enhance immune efficacy induced by Ag85A DNA vaccination

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    内容提示： 1 CD226 as a Genetic Adjuvant to Enhance Immune Efficacy Induced by Ag85A DNA Vaccination At this time, the DNA vaccine containing Ag85A does not induce intensive immune responses or provide efficacious protection. Although a DNA vaccine can generate protective immunity against infectious pathogens, some previous reports have also indicated that plasmid DNA vaccines encoding a single antigen do not induce Yan LI1,2, Xun SUN1, Changlong LU1 (1. Department of Immunology, China Medical University, Shenyang...

    文档格式：PDF | 页数：13 | 浏览次数：131 | 上传日期：2015-10-30 16:40:29 | 文档星级：
    1 CD226 as a Genetic Adjuvant to Enhance Immune Efficacy Induced by Ag85A DNA Vaccination At this time, the DNA vaccine containing Ag85A does not induce intensive immune responses or provide efficacious protection. Although a DNA vaccine can generate protective immunity against infectious pathogens, some previous reports have also indicated that plasmid DNA vaccines encoding a single antigen do not induce Yan LI1,2, Xun SUN1, Changlong LU1 (1. Department of Immunology, China Medical University, Shenyang, 110001, China; 2. Department of Immunology and Microbiology, Liaoning College of Health Vocational Technology, Shenyang, 110101, China) Abstract: Antigen-85A (Ag85A) is one of the major proteins secreted by Mycobacterium tuberculosis. Many studies on animal models have shown that vaccination with the recombinant Ag85A-DNA or Ag85A protein induces powerful immune response. However, these vaccines cannot induce sufficient protective immune response in the systemic compartment. CD226, a member of the immunoglobulin superfamily, is mainly expressed on NK cells, T cells, monocytes and platelets, and can be served as a co-stimulator that contributes to multiple innate and adaptive immune responses. GM-CSF is an effective genetic adjuvant that increases Ag85A immunogenicity to enhance the activity of cytotoxic T lymphocytes (CTLs) in mice immunized with recombinant pRSC-Ag85A-GM-CSF plasmid DNA. However, there has been no study showing that either CD226 protein or DNA has been used as an adjuvant for vaccine development. The aim of this study was to develop a novel Ag85A DNA vaccine with CD226 as the genetic adjuvant to increase the immune efficacy of Ag85A. Oral vaccination with pcDNA3.1- Ag85A-CD226 DNA induced potent immune responses in mice. CD226 was an effective genetic adjuvant that improved the immune efficacy of Ag85A and enhanced the activity of CTLs and NK cells in mice. Our results suggest that CD226 is an effective adjuvant to enhance the immune efficacy of Ag85A. Our findings provide a new strategy for the development of a DNA vaccine co-expressing Ag85A and CD226 against tuberculosis and tumors. Keywords: Ag85A, CD226, genetic adjuvant, DNA vaccine 1 INTRODUCTION Antigen-85A (Ag85A) of family Ag85 is a major protein secreted by mycobacterium species that participates in synthesis of mycolic acid in cell walls[1]. Ag85A induces substantial Th1 cell proliferation and vigorous Th1 cytokine production in humans and mice infected with mycobacteria, including individuals vaccinated with BCG[2]. Mice vaccinated with plasmid DNA containing the Ag85A gene exhibit elevated IL-2, IFN-γ and IgG2a production, as well as cytotoxic T lymphocyte (CTL) activity in response to BCG proteins, of which Ag85A is a major component[3-4]. Oral vaccination with pcDNA3.1-Ag85A DNA induces antigen specific mucosal, cellular, and humoral immune responses in mice[5]. In addition, a dendritic cell vaccine modified by the Ag85A gene enhances anti-tumor immunity against bladder cancer by up-regulating cellular immune responses[6]. Author Biography: LI Yan, female, Ph.D., lecturer. Research direction: Mucosal immunity and tumor immunity. E-mail, licaorenyanyan@163.com; Tel: 86-024-23256666-5345

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