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首页> 外文学位 >Development of new tools for foreign antigen expression in live Vibrio cholerae vaccine strains.
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Development of new tools for foreign antigen expression in live Vibrio cholerae vaccine strains.

机译：开发用于在活霍乱弧菌疫苗株中表达外源抗原的新工具。

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摘要

Live, attenuated Vibrio cholerae vaccines can induce potent immune responses after only a single oral dose. The strategy of harnessing these strains to present antigens from heterologous pathogens to the mucosal immune system in vivo shows great promise. To fully realize this possibility, strains must be created which stably express antigens in vivo in sufficient quantity to generate an immune response. In vivo-induced promoters have been shown to increase stability and immunogenicity of foreign antigens expressed from multicopy plasmids. A recent in vivo expression technology study conducted in humans has identified several potential V. cholerae in vivo-induced promoters, including PargC, PfhuC, and Pvca1008. This study explores the use of these and other promoters in the expression of heterologous proteins from the live attenuated V. cholerae vaccine strain CVD103-HgR. Strains were constructed that express and secrete the D4 subunit of Protective Antigen from Bacillus anthracis and these strains were tested for immunogenicity in vivo. A major roadblock in the testing of new V. cholerae vector vaccines is the lack of a convenient small animal model. Several attempts were made to develop such a model, without great success. However, it was possible to quantify in vivo induction of the promoters using the well characterized suckling mouse model. Indeed, this study used real-time bioluminescent imaging of suckling mice to directly demonstrate high levels of in vivo induction of the V. cholerae promoters, PargC, PfhuC, and Pvca1008.
机译：减毒的霍乱弧菌活疫苗仅单次口服就可以诱导有效的免疫反应。利用这些菌株在体内将来自异源病原体的抗原呈递至粘膜免疫系统的策略显示出巨大的希望。为了完全认识到这种可能性，必须创建能够在体内稳定表达抗原的数量足以产生免疫应答的菌株。体内诱导的启动子已显示增加从多拷贝质粒表达的外源抗原的稳定性和免疫原性。最近在人体中进行的体内表达技术研究已经确定了几种潜在的霍乱弧菌体内诱导的启动子，包括PargC，PfhuC和Pvca1008。这项研究探索了这些启动子和其他启动子在活减毒霍乱弧菌疫苗株CVD103-HgR的异源蛋白表达中的用途。构建了表达和分泌炭疽芽孢杆菌保护性抗原D4亚基的菌株，并测试了这些菌株的体内免疫原性。测试新型霍乱弧菌载体疫苗的主要障碍是缺乏方便的小动物模型。进行了多次尝试来开发这种模型，但均未取得成功。但是，可以使用特征明确的哺乳小鼠模型量化启动子的体内诱导。确实，这项研究使用了乳鼠的实时生物发光成像，直接证明了霍乱弧菌启动子，PargC，PfhuC和Pvca1008的体内高水平诱导。

著录项

  • 作者

    Morin, Cara E.;

  • 作者单位

    University of Maryland, Baltimore.;

  • 授予单位 University of Maryland, Baltimore.;
  • 学科 Biology Molecular.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 134 p.
  • 总页数 134
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 地球物理学;
  • 关键词

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