Filariasis is a major public health problem in a number of developing countries, where there are an estimated 100 million cases of the lymphatic form. One of the major problems in the study of filariasis is the lack of an optimal animal model. The overall goal of the proposed research is to increase our understanding of the immunopathogenesis of lymphatic filariasis through the study of the biology of Brugia malayi infection in the C.B. 17-SCID/SCID mouse (hereinafter referred to as the SCID mouse). In preliminary studies, detailed below, we have found that the SCID mouse will indeed permit the maturation of injected B. malayi larvae to the adult stage. In addition, when the larvae are injected subcutaneously, some migrate to the lymphatics where they give rise to lyphangiectasis, lymphangitis and lymphatic stasis. These observations indicate that B. malayi infection of the SCID mouse may be a good model for human lymphatic filariasis in that it recapitulates several important pathological features of human infection. The present proposal is intended: (1) To more completely document the pathological changes caused by B. malayi infection in the SCID mouse. (2) To determine the fate of B. malayi L3 larvae in SCID mice reconstituted with lymphoid cells or serum from naive, coisogeneic C.B.-17 wild type animals. (3) To use the SCID mouse as a model system to screen the efficacy of potential vaccine candidate antigens identified in the laboratory of the PI using recombinant DNA technology. The long term goal of these studies is to investigate the role of the human immune system in the protection from or pathogenesis of filariasis. The most attractive feature of the SCID mouse is its ability to support the maturation of a human immune system when appropriately reconstituted. The establishment and characterization of the SCID mouse of filiariasis as detailed in this proposal will provide the basis for our future efforts to investigate the role of the human immune response in the pathogenesis of filariasis.
