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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Distinct immune responses to transgene products from rAAV1 and rAAV8 vectors
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Distinct immune responses to transgene products from rAAV1 and rAAV8 vectors

机译：对来自rAAV1和rAAV8载体的转基因产物的独特免疫应答

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摘要

Recently developed serotypes of recombinant adeno-associated virus (rAAV) vectors have significantly enhanced the use of rAAV vectors for gene therapy. However, host immune responses to the transgene products from different serotypes remain uncharacter-ized. In the present study, we evaluated the differential immune responses to the transgene products from rAAV1 and rAAV8 vectors. In non-obese diabetic (NOD) mice, which have a hypersensitive immunity, rAAV serotype 1 vector (rAAV1-hAAT) induced high levels of both humoral and cellular responses, while rAAV8-hAAT did not. In vitro studies showed that rAAV1, but not rAAV8 vector transduced dendritic cells (DCs) efficiently. In vivo studies indicated that vector transduction of DCs was essential for the immune responses; while the presence of a transgene product (or foreign gene product produced by host cells) was not immuno-genic. Intriguingly, preimmunization with rAAV8-hAAT vector or with serum of hAAT transgenic NOD mouse induced immune tolerance to rAAV1-hAAT injection. These results demonstrate the immunogenic differences of rAAV1 and rAAV8 and imply tremendous potential for these vectors in different applications, where an immune response to transgene is to be either elicited or avoided.
机译：最近开发的重组腺相关病毒（rAAV）载体的血清型已大大增强了rAAV载体用于基因治疗的用途。然而，宿主对来自不同血清型的转基因产物的免疫反应仍未表征。在本研究中，我们评估了对来自rAAV1和rAAV8载体的转基因产物的差异免疫反应。在具有超敏免疫力的非肥胖糖尿病（NOD）小鼠中，rAAV血清型1载体（rAAV1-hAAT）诱导了高水平的体液和细胞反应，而rAAV8-hAAT却没有。体外研究表明，rAAV1有效地转导了树突状细胞（DC），而rAAV8载体则没有。体内研究表明，DCs的载体转导对于免疫应答至关重要。转基因产物（或宿主细胞产生的外源基因产物）的存在不是免疫原性的。有趣的是，用rAAV8-hAAT载体或hAAT转基因NOD小鼠血清进行的预免疫诱导了对rAAV1-hAAT注射的免疫耐受。这些结果证明了rAAV1和rAAV8的免疫原性差异，并暗示了这些载体在不同应用中的巨大潜力，在该应用中将引发或避免对转基因的免疫应答。

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  • 作者

    Yuanqing Lu; Sihong Song;

  • 作者单位

    Department of Pharmaceutics, Powell Gene Therapy Center, Genetics Institute, University of Florida, Gainesville, FL 32610;

    Department of Pharmaceutics, Powell Gene Therapy Center, Genetics Institute, University of Florida, Gainesville, FL 32610;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    DC activation; rAAV vectors;

    机译：直流激活rAAV载体;

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