While immune serum antibody has been shown to inhibit Treponema pallidum subsp. pallidum adherence and invasion of host cell monolayers, augment macrophage phagocytosis of treponemes, and kill treponemes in the presence of complement, the relationship of these potential immune mechanisms to the contribution of protective immunity during syphilitic infection has not been established. Using a novel in vitro killing assay developed in the investigator's laboratory, they have demonstrated that T. pallidum binds immune serum antibody within 30 minutes; this bound antibody inhibits treponemal adherence and invasion and has treponemicidal potential. This assay has shown that the slow kinetics of killing are determined by the rate of complement activation and correlate with the aggregation of T. pallidum rare outer membrane protein (TROMP), molecules that the investigator has recently identified by freeze-fracture analysis and that are likely to represent the initial surface exposed targets on this organism. Further, the investigator has shown that treponemicidal activity measured by this assay correlates with the ontogeny of immunity to symptomatic and disseminated infection in experimental rabbit syphilis. Strategies are proposed in this study to use this novel in vitro assay system in combination with experimentally infected rabbits to relate directly complement-dependent treponemicidal activity to TROMP and treponemal adherence and invasion inhibition to the status of immunity during the course of experimental rabbit syphilis.
The specific aims of this study are: 1) relate the ontogeny of immunity in experiment rabbit syphilis and the development of treponemicidal antibody to tROMP, 2) determine the mechanism(s) of antibody-mediated, complement-dependent, in vitro treponemicidal activity, and 3) relate the development of immunity in experimental rabbit syphilis to the inhibition of treponemal adherence and invasion of host cells. It is believed that the results of this study will provide a further understanding of the specific immune mechanisms responsible for acquired resistance against syphilis.
