INFECTIVE LARVAE AND IMMUNITY IN FILARIASIS

该项目旨在解决人类保护性免疫的重要问题， 淋巴丝虫病 这是基于一种普遍的观点，即表面 感染性幼虫（L3）的抗原是 保护性抗丝虫免疫反应。 这个假设是基于 在动物模型中研究丝虫病的结果，并得到以下支持： 其他蠕虫寄生虫的经验。 不幸的是，免疫学 对丝虫L3的研究受到许多因素的严重阻碍， 技术障碍，其中最重要的是有限的 寄生虫材料的可用性。 本提案的特别优势在于材料和 我们将拥有的资源和我们将使用的方法 在该项目中雇用。 我们计划进行一系列协调的研究， 严格评估L3表面抗原在保护性免疫中的作用 对人类丝虫病原体马来丝虫和班氏吴策线虫的作用。 我们 将识别和表征L3表皮抗原， 保护性免疫反应的目标。 我们将研究 流行区人血清中抗L3表面抗原的抗体。 我们 将产生针对L3表面抗原的多克隆和单克隆抗体， 我们将利用重组DNA技术， 分析和用于免疫研究的决定因素。 体内 将进行研究以检查被动施用的能力， 单克隆抗体或用重组抗原主动免疫， 在啮齿动物丝虫病中赋予对丝虫L3攻击的保护性免疫 模型 我们希望这些研究将有助于最终的发展 有效的丝虫病疫苗

This project addresses the important issue of protective immunity in human lymphatic filariasis. It is based on the widely held view that surface antigens of infective larvae (L3) are critically important targets for protective antifilarial immune responses. This hypothesis is based on results from studies of filariasis in animal models, and it is supported by experience with other helminth parasites. Unfortunately, immunological studies of filarial L3 have been severely handicapped by a number of technical hurdles, the most important of which has been limited availability of parasite material. The special strengths of the present proposal are the materials and resources that we will have at our disposal and the methods that we will employ in the project. We have planned a coordinated series of studies to critically evaluate the role of L3 surface antigens in protective immunity to the human filarial pathogens Brugia malayi and Wuchereria bancrofti. We will identify and characterize L3 cuticular antigens which are potential targets for protective immune responses. We will study the prevalence of antibodies to L3 surface antigens in human sera from endemic areas. We will produce polyclonal and monoclonal antibodies to L3 surface antigens, and we will use recombinant DNA methodology to produce L3 surface antigenic determinants for analysis and for use in immunization studies. In vivo studies will be performed to examine the ability of passively administered monoclonal antibodies or active immunization with recombinant antigen to confer protective immunity to filarial L3 challenge in rodent filariasis models. We hop these studies will contribute to the eventual development of effective vaccines for filariasis.