The adverse consequences of infection on the reproductive health of women is the principal reason for the importance of gonococcal infection as a health problem. Most of these consequences result from gonococcal infection of the upper genital tract with resultant salpingitis and subsequent, tubo-ovarian abscess, infertility and ectopic pregnancy. The pathogenesis of gonococcal salpingitis, particularly the role of human immune responses in its prevention, is poorly understood. Recent in vitro studies indicate that the gonococcal opacity proteins (Opa) play a key role in inducing endocytosis by mucosal cells, a process which may be necessary for the establishment of infection in the submucosa and ultimately salpingitis. Our studies among sex workers in Nairobi, Kenya indicate that antibody to Opa variants is correlated with a substantial reduction in the risk of salpingitis among women with gonococcal cervical infection. Together these data suggest that Opa plays a key in the development of gonococcal salpingitis and that immune responses to Opa may be protective. In the studies outline in this submission, we propose to examine the role of Opa in the pathogenesis of gonococcal salpingitis and further characterize potentially protective immune responses to Opa. In studies conducted among sex worker and non-sex worker populations in Nairobi, we propose to: 1) determine the epitope specificity of antibody to Opa which is correlated with protection against gonococcal salpingitis. 2) examine the role of antibody to the Opa species expressed by homologous infecting strains in protecting against gonococcal salpingitis. 3) examine the role of genital tract antibody to Opa in mediating protection against gonococcal salpingitis. 4) compare Opa expression in gonococci isolated from the endocervix and endometrium. 5) determine if antibody to Opa correlates with protection against gonococcal salpingitis in non-sex worker populations. These studies will further our understanding of the role of Opa in the pathogenesis of gonococcal salpingitis and the role of Opa specific immune responses in protection against salpingitis.
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