It is here proposed to study the molecular basis of parasite-vector interactions in the Brugia malayi - Aedes aegypti model. B. malayi was chosen for study because, of the three agents of human lymphatic filariasis, it is the most readily maintained in the laboratory, offering a complete model for transmission of the infection. These studies will focus on developmentally-regulated microfiliarial functions which are critical to transmission. Three basic questions will be considered: 1) How does microfiliarial maturation in the vertebrate host affect the worm's capacity to infect the mosquito? 2) What is the biochemical basis of this maturation? and 3) Can molecules critical to microfilarial-vector interactions be defined using monoclonal antibodies, and can these antibodies directly interfere with parasite development in the vector? To answer these questions, microfilariae of different age groups will be compared for their capacity to perform successive steps in the infective process. These functional analyses will then be correlated with biochemical and antigenic differences among the different age groups, as determined by analytical electrophoresis, Western blot analysis, and other techniques. If particular biochemical changes are found to accompany the acquisition of function (ability to successfully interact with the vector), then monoclonal antibodies of appropriate specificity will be tested for their ability to alter these parasite-vector interactions. By providing a manipulable model for filarial development in arthropod vectors, these experiments will further understanding of the mechanics of transmission of filarial infection, potentiate the development of in vitro culture systems for infective stage larvae, and elucidate general mechanisms of differentiation and development in parasitic nematodes.
| Dissanayake, S; Perler, F B; Xu, M et al. (1995) Differential recognition of microfilarial chitinase, a transmission-blocking vaccine candidate antigen, by sera from patients with Brugian and Bancroftian filariasis. Am J Trop Med Hyg 53:289-94 |
| Fuhrman, J A; Lane, W S; Smith, R F et al. (1992) Transmission-blocking antibodies recognize microfilarial chitinase in brugian lymphatic filariasis. Proc Natl Acad Sci U S A 89:1548-52 |
| Fuhrman, J A; Piessens, W F (1989) A stage-specific calcium-binding protein from microfilariae of Brugia malayi (Filariidae). Mol Biochem Parasitol 35:249-57 |
