INFECTIVE LARVAE AND IMMUNITY IN FILARIASIS

该项目解决了人体保护性免疫的重要问题

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.