Lustigman Sara, MacDonald Angus J, Abraham David
Laboratory of Molecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood Center, 310 E 67th Street, New York, NY 10021, USA.
Int J Parasitol. 2003 Sep 30;33(11):1161-71. doi: 10.1016/s0020-7519(03)00170-x.
Onchocerciasis is a major filarial disease and is the second most common cause of infectious blindness in the world. Disease development after infection with Onchocerca volvulus varies widely and is determined by the host's immune response to the parasite. Vector control and administration of ivermectin has reduced infection and disease rates significantly. However, limitations of these programmes, including ivermectin's selective activity on microfilariae, the need for 10-15 years of annual treatments, logistical obstacles and the potential emergence of drug-resistant strains demand alternative strategies. A vaccine that targets O. volvulus infective third-stage larvae (L3) could provide an additional tool to guarantee successful elimination of infection with O. volvulus. An essential step in the development of immunoprophylactic procedures and reagents is the identification of host immune responses toward antigens of O. volvulus L3 and L3 developing to the fourth-stage larvae that are associated with protection against these stages of the parasite. This review summarises the recent advancements in understanding the immune mechanisms in particular the CD4(+) responses to L3 stages in humans and in the mouse vaccination model. Comparison between the two uncovered common immunological elements in naturally exposed humans and mice vaccinated with radiation attenuated L3 or recombinant O. volvulus antigens, as well as significant differences. These studies promisingly suggest that the O. volvulus mouse model is a very useful adjunct to the studying of natural infection in humans and could provide us with the tools to identify the target molecules and the effector immune correlates of protection in humans responsible for attrition of L3 stages. Since some of these antigens may exist in other nematodes, any insight gained into the mechanisms of vaccine-induced anti-O. volvulus L3 protective immunity in both humans and mice could be applicable to the development of vaccines against other nematode infections.
盘尾丝虫病是一种主要的丝虫病，是全球第二大常见的感染性失明病因。感染旋盘尾丝虫后的疾病发展差异很大，由宿主对该寄生虫的免疫反应决定。病媒控制和伊维菌素给药已显著降低了感染率和发病率。然而，这些项目存在局限性，包括伊维菌素对微丝蚴的选择性活性、需要连续10 - 15年每年进行治疗、后勤障碍以及耐药菌株可能出现，这就需要替代策略。一种针对旋盘尾丝虫感染性第三期幼虫（L3）的疫苗可以提供额外的工具，以确保成功消除旋盘尾丝虫感染。免疫预防程序和试剂开发的一个关键步骤是确定宿主针对旋盘尾丝虫L3抗原以及发育至第四期幼虫的L3的免疫反应，这些反应与针对寄生虫这些阶段的保护相关。本综述总结了在理解免疫机制方面的最新进展，特别是人类和小鼠疫苗接种模型中对L3阶段的CD4(+)反应。两者之间的比较揭示了自然暴露的人类和接种辐射减毒L3或重组旋盘尾丝虫抗原的小鼠中共同的免疫元素，以及显著差异。这些研究有希望表明，旋盘尾丝虫小鼠模型对于研究人类自然感染是一个非常有用的辅助工具，并且可以为我们提供工具来识别负责L3阶段消耗的人类中的靶分子和保护性免疫效应相关物。由于其中一些抗原可能存在于其他线虫中，对疫苗诱导的抗旋盘尾丝虫L3保护性免疫在人类和小鼠中的机制所获得的任何见解都可能适用于开发针对其他线虫感染的疫苗。
