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首页> 外文期刊>Infection and immunity >Vervet Monkeys Vaccinated with Killed Leishmania major Parasites and Interleukin-12 Develop a Type 1 Immune Response but Are Not Protected against Challenge Infection
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Vervet Monkeys Vaccinated with Killed Leishmania major Parasites and Interleukin-12 Develop a Type 1 Immune Response but Are Not Protected against Challenge Infection

机译:接种了杀死的利什曼原虫主要寄生虫和白介素12的黑长尾猴会产生1型免疫反应,但不能抵抗挑战性感染

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Leishmania major is a protozoan parasite that causes chronic cutaneous lesions that often leave disfiguring scars. Infections in mice have demonstrated that leishmanial vaccines that include interleukin-12 (IL-12) as an adjuvant are able to induce protective immunity. In this study, we assessed the safety, immunopotency, and adjuvant potential of two doses of IL-12 when used with a killed L. major vaccine in vervet monkeys. The induction of cell-mediated immunity following vaccination was determined by measuring delayed-type hypersensitivity, in vitro lymphocyte proliferation, and gamma interferon (IFN-γ) production. Protection was assessed by challenging the animals with L. major parasites and monitoring the course of infection. At low doses of IL-12 (10 μg), a small increase in the parameters of cell-mediated immunity was observed, relative to those in animals that received antigen without IL-12. However, none of these animals were protected against a challenge infection. At higher doses of IL-12 (30 μg), a substantial increase in Leishmania-specific immune responses was observed, and monkeys immunized with antigen and IL-12 exhibited an IFN-γ response that was as great as that in animals that had resolved a primary infection and were immune. Nevertheless, despite the presence of correlates of protection, the disease course was only slightly altered, and protection was low compared to that in self-cured monkeys. These data suggest that protection against leishmaniasis may require more than the activation of Leishmania-specific IFN-γ-producing T cells, which has important implications for designing a vaccine against leishmaniasis.
机译:主要利什曼原虫是一种原生动物寄生虫,可引起慢性皮肤损伤,并经常留下毁容性的疤痕。小鼠感染已表明,包括白介素12(IL-12)作为佐剂的利什曼疫苗能够诱导保护性免疫。在这项研究中,我们评估了与灭活的L一起使用时,两剂IL-12的安全性,免疫力和佐剂潜力。黑长尾猴的主要疫苗。通过测量迟发型超敏反应,体外淋巴细胞增殖和γ-干扰素(IFN-γ)的产生来确定接种疫苗后细胞介导的免疫的诱导。通过用 L攻击动物来评估保护。主要寄生虫并监测感染过程。相对于接受不含IL-12抗原的动物,在低剂量的IL-12(10μg)下,观察到细胞介导的免疫参数略有增加。但是,这些动物都没有受到攻击感染的保护。在较高剂量的IL-12(30μg)下,观察到利什曼原虫特异性免疫反应显着增加,并且用抗原和IL-12免疫的猴子表现出的干扰素就像已经解决了原发感染并且具有免疫力的动物一样。尽管如此,尽管存在保护作用的相关性,但疾病进程仅略有改变,并且与自愈猴子相比,保护作用较低。这些数据表明,针对利什曼病的保护作用可能比激活利什曼病特异的产生IFN-γ的T细胞需要更多的时间,这对于设计针对利什曼病的疫苗具有重要意义。

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