Immunization with Genetically Modified Trypanosomes Provides Protection against Transmissible Spongiform Encephalopathies.
Immunization with Genetically Modified Trypanosomes Provides Protection against Transmissible Spongiform Encephalopathies.
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DOI：
10.3390/ijms231810629
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发表时间：
2022-09-13
影响因子：
5.6
通讯作者：
Xanthopoulos, Konstantinos
中科院分区：
文献类型：
--
作者：
Triller, Gianna;Garyfallos, Dimitrios A.;Papavasiliou, F. Nina;Sklaviadis, Theodoros;Stavropoulos, Pete;Xanthopoulos, Konstantinos
传染性海绵状脑病是一种无法治愈的神经退行性疾病，与生理性蛋白转化为与疾病相关的蛋白有关。尽管针对传染性海绵状脑病的免疫已显示出巨大的潜力，但免疫耐受效应阻碍了主动免疫方案的成功预防。在这项研究中，我们评估了锥体作为生物平台向宿主免疫系统呈递Pron抗原肽的作用。在不使用佐剂的情况下，在免疫方案中使用经过改造的锥虫，可以在野生型小鼠中产生针对普恩蛋白的体液免疫反应，而没有出现不良反应。该方案引发的免疫反应在体外显示出治疗潜力，并在生物测定中进一步评估，在具有代表性的普恩病毒病小鼠模型中，免疫小鼠受到部分保护。进一步的研究正在进行中，以更好地描述免疫反应并优化免疫方案。
Transmissible spongiform encephalopathies are incurable neurodegenerative diseases, associated with the conversion of the physiological prion protein to its disease-associated counterpart. Even though immunization against transmissible spongiform encephalopathies has shown great potential, immune tolerance effects impede the use of active immunization protocols for successful prophylaxis. In this study, we evaluate the use of trypanosomes as biological platforms for the presentation of a prion antigenic peptide to the host immune system. Using the engineered trypanosomes in an immunization protocol without the use of adjuvants led to the development of a humoral immune response against the prion protein in wild type mice, without the appearance of adverse reactions. The immune reaction elicited with this protocol displayed in vitro therapeutic potential and was further evaluated in a bioassay where immunized mice were partially protected in a representative murine model of prion diseases. Further studies are underway to better characterize the immune reaction and optimize the immunization protocol.
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影响因子：
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通讯作者：
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