We propose to apply molecular biological techniques towards an understanding of some aspects of the biology of the parasites causing lymphatic filariasis, and at the same time determine the structure of antigenic molecules that might be important in protective immunity. The specific objectives will be: 1. ANALYSIS OF MOULTING: We will clone the genes encoding moulting enzymes, by exploiting the conservation of physiology and biochemistry of the process of moulting among nematodes. These genes will be used to study the enzymology of moulting, the regulation of synthesis of these enzymes and potential strategies for interfering with this process. The goal of this set of experiments is to determine whether specific immunization against moulting enzymes is a viable strategy for blocking morphogenesis of the filarial parasites. 2. ANALYSIS OF CUTICULAR COLLAGENS: We will use a partial collagen gene we have recently cloned to isolate full length collagen genes and analyze their stage-specific expression and sequence diversity. The goal of this set of experiments is two fold: first to define whether there are any collagens that are specific for the L3 and L4 stages of the parasite and second to determine nematode specific sequences that are not shared with mammalian collagen. Immunization with L3 and/or L4 specific collagen sequences that are structrually different from host collagen may be effective means of eliciting protective immunity without the danger of autoimmune responses. 3. CLONING GENES FOR PROTECTIVE ANTIGENS: We will screen cDNA and genomic expression libraries derived from the human filarial parasite B. malayi with sera from patients suffering from a wide spectrum of filarial disease to isolate genes encoding protective antigens. We have used a serum from a patient suffering from Tropical Pulmonary Eosinophilia (TPE) to isolate several reactive gt-11 clones and have sequenced the inserts in two of them. These studies will be extended during the tenure of this proposal.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Unknown (R22)
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Tropical Medicine and Parasitology Study Section (TMP)
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University of Connecticut
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Rajan, T V; Gundlapalli, A V (1997) Lymphatic filariasis. Chem Immunol 66:125-58
Schmitz, K A; Hale, T J; Rajan, T V et al. (1996) Localization of paramyosin, myosin, and a heat shock protein 70 in larval and adult Brugia malayi. J Parasitol 82:367-70
Rajan, T V; Greiner, D L; Yates, J A et al. (1996) Growth of the human filarial parasite Brugia malayi in mice lacking major histocompatibility complex class II antigen expression. Acta Trop 61:267-71
Greiner, D L; Shultz, L D; Yates, J et al. (1995) Improved engraftment of human spleen cells in NOD/LtSz-scid/scid mice as compared with C.B-17-scid/scid mice. Am J Pathol 146:888-902
Yates, J A; Schmitz, K A; Nelson, F K et al. (1994) Infectivity and normal development of third stage Brugia malayi maintained in vitro. J Parasitol 80:891-4
Green, D F; Yates, J A (1994) Microscopic visualization of Wuchereria and Brugia larval stages in intact cleared mosquitoes. Am J Trop Med Hyg 51:483-8
Rajan, T V; Nelson, F K; Killeen, N et al. (1994) CD4+ T-lymphocytes are not required for murine resistance to the human filarial parasite, Brugia malayi. Exp Parasitol 78:352-60
Rajan, T V; Bailis, J M; Yates, J A et al. (1994) Maternal influence on susceptibility of offspring to Brugia malayi infection in a murine model of filariasis. Acta Trop 58:283-9
Rajan, T V; Nelson, F K; Shultz, L D et al. (1994) Influence of gonadal steroids on susceptibility to Brugia malayi in scid mice. Acta Trop 56:307-14
Rajan, T V; Nelson, F K; Cupp, E et al. (1992) Survival of Onchocerca volvulus in nodules implanted in immunodeficient rodents. J Parasitol 78:160-3

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