HUMORAL AND CELLULAR IMMUNE RESPONSES IN GONOCOCCAL DISEASE

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Gonorrhea is one of the most common sexually transmitted diseases in the US. Gonococcal infections cause significant morbidity. Sequelae associated with gonorrhea can include tubal scarring after pelvic inflammatory disease, and subsequent increase in ectopic pregnancy and infertility. Little is known about the immune response to this organism and even less is known about what defines a protective anti-gonococcal immune response. We have a Sexually Transmitted Disease Clinic that is well established in our urban community with a system in place for excellent contact tracing and follow-up. This infrastructure will allow us to obtain a cohort of patients with gonococcal infection and their infected and uninfected contacts to discern possible parameters of protection as defined by their anti-gonococcal immune response. We propose to measure the antibody response in uninfected and infected contacts to patients with gonococcal infection towards the gonococcal porin (Protein I or Por), the gonococcal reduction modifiable protein (protein III or Rmp), and gonococcal lipooligosaccharide (LOS). We will also measure the ability of Por and Rmp to stimulate isolated peripheral blood mononuclear cells (PBMC - mainly consisting of lymphocytes) obtained from these groups of patients. The anti-gonococcal humoral and lymphocyte immune response in infected contacts will be compared to the response in uninfected contacts to determine if any of the responses correlates to potential protection from gonococcal infection. Moreover, PBMC stimulation and antibody response will be compared to determine if they are associated and whether PBMC stimulation by the proteins is a more sensitive measurement of an immune response to gonococcal antigens than antibody production. We will utilize the patients T lymphocytes to derive T cell clones and map Por and Rmp specific T cell epitopes. If there is a difference in the Por and Rmp T cell epitopes recognized by uninfected contacts as compared to the uninfected contacts and between the uninfected contacts as compared to their infected primary partners, we could then determine if recognition (or lack of recognition) of certain epitopes correlate with protection from gonococcal infection. These potentially "protective" T cell epitopes would be possible anti-gonococcal vaccine candidates.