The University of Washington STD CRC involves a consortium with Harvard University and the Universities of Manitoba and Nairobi. The central theme remains prevention of female reproductive tract morbidity, with a secondary theme of defining STD/HIV interactions - through multidisciplinary research on sexual behavior; on the clinical epidemiology, immunobiology, and pathogenesis of gonococcal and chlamydial infections; and on the clinical epidemiology of human papillomavirus (HPV) and human herpes virus 8 (HHV8) infections. This proposal includes four interrelated projects and two scientific cores. The first Project, CTL and Immunology of Chlamydia, has demonstrated that CTL priming produces cross-reactive partial immunity to C. trachomatis in a murine model;
and aims to identify the chlamydia antigens that produce the CTL response and test suitability of these antigens to engender protective immunity using a recombinant anthrax toxin vaccine delivery system. The second Project, Chlamydial and Gonococcal Infection: Immunobiology in the Female Reproductive Tract combines the work now carried out in cohort studies of Nairobi female sex workers, and aims to examine the role of mucosal and systemic immune responses in mediating resistance and susceptibility to gonococcal and chlamydial infection and disease; and to examine how these two infections alter women's immune responses to other STI. The third Project, Sexual Behavior and STD in Adolescents and Young Adults, continues examination of how characteristics of sexual mixing and partnerships influence STD occurrence, and extends these studies to a nationally representative sample in the National Longitudinal Study of Adolescent Health (Add Health, N=20,000). A representative subset of Add Health females 17-22 years old will be screened for genital HPV shedding; and the Wave III Add Health Survey Instrument will be applied to adolescents and young adults with STD symptoms or exposure seen in Seattle, St. Louis, and New Orleans, allowing regional comparisons of same-age STD patients with the national sample. In addition, Seattle studies of sexual mixing and STD have been extended to individuals with STD seen in the private health care sector, and to men who have sex with men (MSM). The fourth Project, Human Herpesvirus 8: Epidemiology and Natural History , will determine the prevalence, incidence, and risk factors for acquisition of HHV8 in cohorts of MSM in Seattle & San Francisco, (assessing the impact of a behavioral intervention on HHV-8 acquisition) and in Nairobi female sex workers will assess reservoirs for HHV8 infection and shedding, and its mode of transmission; and will continue clinical and virological characterization of primary HHV8 infection. All projects are interactive, supporting goals of mutual interest: The second Project will provide endometrial specimens for isolation and characterization of human CTL for studies of chlamydial antigen recognition in the first Project The third Project will provide behavioral research collaboration for the second and fourth Projects; and the fourth Project will utilize the Nairobi sex worker cohort from the second Projects.
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