We have developed a rabbit Lyme Disease model in which early erythema migrans (EM) lesions and disseminated infection occur and in which complete infection-derived immunity results. The long term - objectives of this study are to determine protective and pathological immune mechanisms operative during the course of rabbit infection with Borrelia burgdorferi (Bb). The rabbit model of Lyme disease provides a unique opportunity to address local and disseminated disease manifestations similar to those in human infection, and to address the cellular and humoral immune mechanisms in infection-derived immunity. Specific and cross-reactive immunity to challenge will be determined utilizing several well-defined strains. The in situ localization and fate of Bb in skin following intradermal challenge will be correlated with the presence and distribution of PMN's, B cells, and T cell subsets both in situ and in peripheral blood. correlations with acquired resistance will also be made with in vitro lymphocytic cell proliferative responses and humoral immune responses including quantitative ELISA and Western blot analysis, passive protection, opsonophagocytosis, complemet-dependent borreliacidal activity, adherence inhibition, and freeze-fracture electron microscopy for the detection of antibody against Bb outer membrane proteins. The rabbit model will also be employed to address the efficacy of Bb challenge following vaccination with OspA, OspB, an avirulent Bb OspA- and OspB-less mutant, and with a recombinant gene product encoding an exported plasmid protein antigen (EppA). The cellular and humoral arms of the immune response as it relates to the development and healing of the EM lesion will also be addressed utilizing the above described procedures. Further, continued persistence, location, and subsequent elimination of the spirochete after EM healing will be determined by specific in situ analysis. Passive protection studies will be conducted with serum obtained at the time of Bb clearance from the skin in order to determine the immune status of these animals. The possibility of exotoxin in EM formation will be determined by injecting rabbits intradermally with concentrated supernatants from in vitro Bb cultures and by the use of filtrates prepared and concentrated from surgically implanted subcutaneous chambers containing Bb. The rabbit model permits the elucidation of those mechanisms that control persistence versus elimination in tissues to which the organism has disseminated. Studies directed toward the elucidation of dermatotropic, arthritogenic, and/or neurotropic strains utilizing several isolates of Bb are proposed and should contribute toward our understanding of chronicity in humans.
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