INFECTIVE LARVAE AND IMMUNITY IN FILARIASIS

该项目解决了人类保护性免疫的重要问题。 淋巴丝虫病。它是基于普遍持有的观点，即表面 感染性幼虫(L3)的抗原是至关重要的靶标 保护性抗丝虫病免疫反应。这一假设是基于 在动物模型中对丝虫病的研究结果，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的研究受到了一些严重阻碍 技术障碍，其中最重要的是有限的 寄生虫材料的可用性。 本提案的特殊优点是材料和 我们将拥有的资源以及我们将采取的方法 受雇于该项目。我们计划了一系列协调一致的研究，以 严谨评价L3表面抗原在保护性免疫中的作用 对人类丝虫病病原体马来丝虫和班克罗夫氏舞蹈菌。我们 将识别和表征潜在的L3角质层抗原 保护性免疫反应的靶标。我们将研究这种疾病的流行情况 流行区人群血清中的L3表面抗原抗体。我们 会产生针对L3表面抗原的多克隆和单克隆抗体， 我们将使用重组DNA方法来生产L3表面抗原 免疫研究中用于分析和使用的决定因素。活体内 将进行研究，以检验被动给药的能力 用重组抗原进行单抗或主动免疫 啮齿动物丝虫病对丝虫病L3攻击的保护性免疫 模特们。我们希望这些研究将为最终的发展做出贡献 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.