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首页> 外文学位 >Evaluation of low dose exposure and immunogenicity of transgenic maize expressing the Escherichia coli heat-labile toxin B subunit when fed intermittently and daily.
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Evaluation of low dose exposure and immunogenicity of transgenic maize expressing the Escherichia coli heat-labile toxin B subunit when fed intermittently and daily.

机译：间歇性和每日饲喂表达大肠杆菌热不稳定毒素B亚基的转基因玉米的低剂量暴露和免疫原性评估。

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摘要

Transgenic maize expressing the non-toxic B subunit of the Escherichia coli heat-labile toxin (LT-B) in seed has proven to be an effective oral immunogen in mice. Currently, there is considerable concern over accidental consumption of transgenic maize expressing LT-B by humans and domestic animals. While consuming maize-expressed LT-B appears to have no toxic side effects, we have yet to define nonimmunogenic levels of transgenic LT-B when ingested. We also intend to determine if accidental exposure to LT-B could affect a later response to a vaccine containing LT-B as either an antigen or a carrier.; Our first goal was to determine the largest dose of LT-B orally administered in mice that does not result in a measurable immune response. Mice were fed low doses of LT-B intermittently (days 0, 7 and 21) resembling vaccine dose scheduling. To determine the effects of previous exposure on vaccine administration, we fed mice intermittently or daily for 28 days to resemble two distinct inadvertent exposure scenarios. We subsequently boosted all mice with vaccine-level doses of LT-B. To determine immune responses, serum and fecal pellets were collected weekly for measurement of LT-B-specific antibodies.; Mice fed 0.02 microg LT-B intermittently demonstrated immune priming in 62.5% of the animals. Mice that were fed ≤0.002 microg LT-B showed no increase in specific antibody nor did they demonstrate immune priming, thus indicating that 0.002 microg LT-B was the highest nonimmunogenic dose tested. Mice that were exposed to maize-derived LT-B, whether daily or intermittently, generate dose-dependent antibody responses to LT-B. All animals that had been previously exposed to LT-B by either intermittent or daily feeding responded strongly to the vaccine-like booster doses, indicating that mice orally exposed to LT-B do not develop oral tolerance to LT-B. Thus, inadvertent oral exposure to LT-B may not negatively impact future vaccinations containing LT-B as either an antigen or carrier.
机译：已证明在种子中表达大肠杆菌热不稳定毒素（LT-B）的无毒B亚基的转基因玉米是小鼠中有效的口服免疫原。当前，人们和家畜对食用表达LT-B的转基因玉米的误用引起了极大的关注。虽然食用玉米表达的LT-B似乎没有毒性副作用，但我们尚未定义摄入时转基因LT-B的非免疫原性水平。我们还打算确定意外暴露于LT-B是否会影响对含有LT-B作为抗原或载体的疫苗的以后反应。我们的首要目标是确定在小鼠中口服最大剂量的LT-B不会导致可测量的免疫反应。类似于疫苗剂量安排，间歇性地向小鼠喂饲低剂量的LT-B（第0、7和21天）。为了确定以前的暴露对疫苗接种的影响，我们间歇或每天喂食小鼠28天，类似于两种不同的无意暴露情况。我们随后用疫苗水平剂量的LT-B加强了所有小鼠的免疫力。为了确定免疫应答，每周收集血清和粪便沉淀以测量LT-B特异性抗体。断续喂0.02微克LT-B的小鼠在62.5％的动物中表现出免疫引发作用。饲喂≤0.002microg LT-B的小鼠未显示特异性抗体的增加，也未显示免疫引发作用，因此表明0.002 microg LT-B是测试的最高非免疫原性剂量。每天或间断暴露于玉米衍生的LT-B的小鼠都会产生对LT-B的剂量依赖性抗体反应。以前通过间歇或每日喂养暴露于LT-B的所有动物对疫苗样的加强剂量反应强烈，这表明口服LT-B的小鼠对LT-B没有口服耐受性。因此，无意中口服LT-B可能不会对将来含有LT-B作为抗原或载体的疫苗产生负面影响。

著录项

  • 作者

    Beyer, April Jean.;

  • 作者单位

    Iowa State University.$bAnimal Science.;

  • 授予单位 Iowa State University.$bAnimal Science.;
  • 学科 Agriculture Animal Culture and Nutrition.; Agriculture Animal Pathology.; Biology Veterinary Science.
  • 学位 M.S.
  • 年度 2007
  • 页码 96 p.
  • 总页数 96
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 饲料;动物医学（兽医学）;动物学;
  • 关键词

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