TROPICAL DISEASE RESEARCH UNIT

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The overall objective of this renewal application for a Tropical Disease Research Unit is to examine specific molecular events critical to development and function of filarial parasites and Schistosoma mansoni and apply this knowledge and associated technologies to the design of anti- helminthic vaccines. The current application is a mutlidisciplinary collaborative program that integrates the scientific approaches nad technical tools of immunology, molecular biology, biochemistry, cell biology, and parasitology applied to study specific aspects of lymphatic filariasis and schistosomiasis mansoni. The specific aims of the four projects included are to: Project 1 . Define specific epitopes of a recombinant filarial antigen which induce protective immunity against B. malayi infection. 2. Elucidate the immune mechanisms by which protective filarial antigens induce resistance. Project 2 1. Define the genes in B. malayi and Ascaris which give rise to transcripts which are trans-spliced. 2. Define the sequence elements which direct initiation and termination of the short non-polyadenylated RNA from which the spliced leader exon is derived. Project 3 1. Define the biochemical structure and clone a 68K protective S. mansoni antigen. 2. Elucidate the immunologic basis of 68K vaccine-induced resistance and determine methods to enhance its efficacy. Project 4 1. Characterize the biochemical nature of the S. mansoni cercarial glycocalyx. 2. Study the mechanisms of glycocalyx release during transformation of cercariae to schistosomula. These projects are based on studies in experimental animals and sera from human volunteers and utilize in vitro manipulation of the causative organisms. Achievement of the goals of each is dependent on scientific and technical interactions between Projects 1-2, Projects 1-3, Projects 2-3, and Projects 3-4 and core facilities providing helminths, lymphocytes cloning expertise, and ultrastructure analyses.