Live nonpathogenic parasitic vector as a candidate vaccine against visceral leishmaniasis
Live nonpathogenic parasitic vector as a candidate vaccine against visceral leishmaniasis
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DOI：
10.1128/iai.73.10.6372-6382.2005
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发表时间：
2005-10-01
影响因子：
3.1
通讯作者：
Papadopoulou, B
中科院分区：
文献类型：
--
作者：
Breton, M;Tremblay, MJ;Papadopoulou, B
迄今为止，还没有针对任何形式的利什曼病的经证实的疫苗。减毒活载体的发展在利什曼原虫疫苗接种领域显示出希望，因为这些生物更有效地模拟真实感染的过程，并能引发免疫系统的有效激活。在本研究中，我们研究了一种对人类无致病性的寄生原生动物，利什曼原虫，作为一种有效靶向树突状细胞和淋巴器官的候选活疫苗的潜力，从而增强抗原呈递，从而影响t细胞免疫反应的大小和质量。我们证明了L. tarentolae激活树突状细胞成熟过程，诱导T细胞增殖和γ干扰素的产生，从而使CD4(+) T细胞向Th1细胞表型倾斜。更重要的是，我们发现单次腹腔注射larentolae可以在易感的BALB/c小鼠中引起对多诺瓦利什曼原虫感染的保护性免疫反应。这些结果表明，使用链状乳杆菌作为活疫苗载体可能代表了一种有希望的方法，可以提高候选活疫苗对抗利什曼原虫感染和其他细胞内病原体的有效性和安全性，其中t细胞介导的反应对保护性免疫的发展至关重要。
To date, there are no proven vaccines against any form of leishmaniasis. The development of live attenuated vectors shows promise in the field of Leishmania vaccination because these organisms mimic more effectively the course of real infections and can elicit potent activation of the immune system. In the present study, we investigated the potential of a parasitic protozoan that is nonpathogenic to humans, Leishmania tarentolae, as a live candidate vaccine that efficiently targets dendritic cells and lymphoid organs, thus enhancing antigen presentation and consequently influencing the magnitude and quality of T-cell immune responses. We demonstrated that L. tarentolae activates the dendritic cell maturation process and induces T-cell proliferation and the production of gamma interferon, thus skewing CD4(+) T cells toward a Th1 cell phenotype. More importantly, we found that a single intraperitoneal injection of L. tarentolae could elicit a protective immune response against infectious challenge with Leishmania donovani in susceptible BALB/c mice. These results suggest that the use of L. tarentolae as a live vaccine vector may represent a promising approach for improving the effectiveness and safety of candidate live vaccines against Leishmania infections and possibly other intracellular pathogens for which T-cell mediated responses are critical for the development of protective immunity.