PROTECTIVE IMMUNITY IN HUMANS AGAINST O VOLVULUS LARVAE

据估计，有1800万人感染了螺旋体螺旋体， 将导致100万人视力受损，更多人失明 不只是40万。虽然定期给药伊维菌素 承诺大幅降低皮肤微丝虫病(MF)的密度， 控制程序的严重局限性要求其可用性 可供选择的控制策略，如针对 感染期幼虫(L3)和发育中的第四期幼虫 (LA)。以前的研究已经提供了证据，自然地获得了 对旋毛虫感染的免疫力可发生在人类身上。这 该项目是一项雄心勃勃的尝试，旨在研究 假定免疫(PI)的人，暴露于感染中，但 而不是被感染。对旋毛虫感染的自然免疫力 PI已被证明与TH1类型的细胞 对卵子抗原、成虫提取物进行测试时的反应。然而， 抗L3 TH2型反应被发现与保护相关 在卷叶草鼠扩散室内模型中。此外，还有 有证据表明耐药性也可能是由抗体介导的，以及 PI血清可以识别独特的幼虫阶段特异性蛋白。 我们假设人类的保护性免疫可以通过 幼虫抗原，它独立于免疫反应运行 成体抗原或MF。为了检验这一假设，我们将：1.分析 日本血吸虫对幼虫粗抗原的细胞和体液免疫应答 PI与感染者的比较，从而提供 缺少与保护性免疫反应相关的信息 免疫力，是专门针对感染者的 寄生虫的各个阶段。2.鉴定和克隆幼虫蛋白 以抗L3保护性免疫反应为靶点的PI，然后 分析PI中对相应重组体的免疫应答 蛋白质，以确定将用于 用于免疫和诱导保护的小鼠扩散舱 对抗旋毛虫L3的挑战。重点将放在抗原上 在从L3到L4的蜕皮过程中表达，与之前的许多结果一样 指出这些抗原是潜在的保护性诱导剂 效应器机构的目标。3.测试疫苗的效力 筛选克隆重组抗原。这次会议的主要目标之一是 该项目是为了发现能够诱导保护性的重组蛋白 在小鼠扩散腔模型中的免疫，从而促进了 开发一种人用疫苗。这些研究应该， 因此，在开发疫苗方面发挥重要作用。 预期临床应用的盘尾丝虫病。

An estimated 18 millions are infected with Onchocerca volvulus which will result in visual impairment in one million and blindness in more than 400,000. Although periodic administration of the drug ivermectin promise a drastic reduction in the densities of skin microfilariae (mf), the severe limitations of the control programs demand the availability of alternative strategies for control, such as vaccines that target the infective stage larvae (L3) and the developing fourth-stage larvae (LA). Previous studies have provided evidence that naturally acquired immunity against O. volvulus infection can occur in humans. This project represents an ambitious attempt to study immunity in the putatively immune (PI) individuals who are exposed to infection but do not become infected. Natural immunity against O. volvulus infection in the PI has been shown to be associated with TH1-type of cellular responses when tested against OvAg, adult worms extracts. However, anti-L3 TH2-type responses were found to be associated with protection in the O. volvulus mouse-diffusion chamber model. In addition, there is some evidence that resistance may be also mediated by antibodies, and that the PI sera can identify unique larval stage-specific proteins. We hypothesize that protective immunity in humans can be elicited by larval antigens, and that it operates independently of immune responses to adult antigens or mf. To test this hypothesis we will: 1. Analyze the cellular and humoral immune responses to crude larval antigens in the PI in comparison to the infected individuals, and thus provide the missing information on immune responses associated with protective immunity and which are directed specifically against the infective stages of the parasite. 2. Identify and clone larval proteins that are targeted by anti-L3 protective immune responses of the PI, and then analyze the immune responses in the PI to the corresponding recombinant proteins in order to determine the candidate molecules to be used in the mouse-diffusion chamber for immunization and the induction of protection against O. volvulus L3 challenge. The emphasis will be on antigens expressed during molting from L3 to L4, as many of the previous results point to those antigens as potential inducer of protection and the target of effector mechanisms. 3. Test the vaccine efficacy of the selected cloned recombinant antigens. One of the major goals of this project is to discover recombinant proteins which can elicit protective immunity in the mouse-diffusion chamber model, and thus advance the development of a vaccine for human use. These studies should, therefore, be instrumental in developing a vaccine against onchocerciasis with anticipated clinical application.