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Production of vaccines and vaccine components in corn.

机译:在玉米中生产疫苗和疫苗成分。

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摘要

Newly emerging infectious agents along with already existing ones, extended lifespan and increased population in the modern age, and the threat of biological warfare increase the demand for high amounts of pharmaceutical/diagnostic recombinant protein production. Plants are safe and cost efficient for production of recombinant pharmaceuticals for humans and livestock. This work investigated potential of corn to serve as a production and delivery vehicle for subunit vaccines and vaccine components. Highly immunogenic antigens LT-B and CT-B from enterotoxigenic strains of Escherichia coli ( E. coli) and Vibrio cholera (V. cholera ) were used in this study as vaccine/component candidates.; This study indicated that corn derived LT-B is capable of inducing immune memory formation. Mice were immunized with LT-B corn through feeding when they were young. They showed a rapid immune memory response in the form of elevated levels of LT-B specific IgG and IgA antibodies upon receiving a booster dose 11 months after initial immunization. This work provided evidence that immunization through feeding with antigens produced in palatable parts of plants would be effective as conventional subunit vaccines in terms of immune memory formation.; The B subunit of cholera toxin (CT-B) was expressed in transgenic corn seeds at high levels. Biochemical and immunological analysis indicated that corn derived CT-B, like the bacterial protein, is assembled into pentamers and binds to GM1 gangliosides. Although the bacterial signal peptide of CT-B appears to not cleaved in corn seed tissue, unlike its counter part LT-B, it is able to induce murine immune system to produce CT-B specific antibodies. This work also provided evidence that administration of a mixture of corn derived CT-B and LT-B together has potential to induce higher levels of specific antibodies than when they were administered alone. This finding opens the possibilities of using these two corn derived antigens in combination and may lead to more efficacious vaccines against both cholera and enderotoxigenic E. coli induced diarrhea.; This work indicated that a major food and feed crop corn holds great potential to be utilized as a production and delivery vehicle for production of vaccine antigens and components which could be used for prevention of both human and animal diseases.
机译:新出现的传染原以及已经存在的传染原,在现代已经延长了寿命并增加了人口,而生物战的威胁也增加了对大量药物/诊断性重组蛋白生产的需求。植物对于生产用于人类和牲畜的重组药物是安全且具有成本效益的。这项工作研究了玉米作为亚单位疫苗和疫苗成分的生产和运输工具的潜力。大肠杆菌(E. coli)和霍乱弧菌(V. cholera)的产肠毒素菌株的高度免疫原性抗原LT-B和CT-B被用作疫苗/候选成分。这项研究表明,玉米衍生的LT-B能够诱导免疫记忆形成。幼鼠通过饲喂LT-B玉米对小鼠进行免疫。他们在初次免疫后11个月接受加强剂量,以LT-B特异性IgG和IgA抗体水平升高的形式表现出快速的免疫记忆反应。这项工作提供了证据,证明通过饲喂植物可口部分产生的抗原进行免疫,将在免疫记忆形成方面作为常规的亚单位疫苗有效。霍乱毒素的B亚基(CT-B)在转基因玉米种子中高水平表达。生化和免疫学分析表明,玉米来源的CT-B与细菌蛋白一样,被组装成五聚体并与GM1神经节苷脂结合。尽管CT-B的细菌信号肽似乎未在玉米种子组织中裂解,但与其对应部分LT-B不同,它能够诱导鼠类免疫系统产生CT-B特异性抗体。这项工作还提供了证据,表明与单独施用相比,将玉米衍生的CT-B和LT-B的混合物一起施用具有诱导更高水平特异性抗体的潜力。这一发现为结合使用这两种玉米来源的抗原开辟了可能性,并可能导致针对霍乱和致雌性大肠杆菌引起的腹泻的更有效的疫苗。这项工作表明,主要的粮食和饲料作物玉米具有巨大的潜力,可以用作生产疫苗抗原和成分的生产和运输工具,从而可以预防人类和动物疾病。

著录项

  • 作者

    Karaman, Sule.;

  • 作者单位

    Iowa State University.;

  • 授予单位 Iowa State University.;
  • 学科 Health Sciences Pharmacology.; Health Sciences Pathology.; Health Sciences Immunology.
  • 学位 Ph.D.
  • 年度 2006
  • 页码 177 p.
  • 总页数 177
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 药理学;病理学;预防医学、卫生学;
  • 关键词

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