IMMUNE RESPONSE TO GONOCOCCAL IRON-REGULATED PROTEINS

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There is a paucity of data regarding immune response to gonococcal antigens induced by mucosal gonococcal disease. The Boston University STD-CRC has been central in elucidating some aspects of the anti- gonococcal immune response. We have previously shown that patients with acute gonorrhea develop both a systemic humoral and a circulating T cell response towards the gonococcal porin, Por. In addition, we have demonstrated that this response might be associated with protection from gonococcal transmission. We wish to extend these studies by investigating the in vivo expression and the immune response in patients with gonorrhea to a group of iron regulated proteins. These include 1) ferric binding protein A (FbpA) a periplasmic transporter of iron that is present in all gonococci, 2) lactoferrin binding protein A (LbpA) required for uptake of iron from lactoferrin, which is the most abundant iron carrying protein in the urogenital mucosa (the environmental niche of the gonococcus) and 3) transferrin binding proteins A and B which are necessary for gonococcal iron uptake from transferrin and are currently being investigated as potential vaccine candidates to prevent both gonococcal and meningococcal infections. Gonococcal iron regulated proteins have been demonstrated to play an essential role in gonococcal pathogenesis. For example,, gonococci that lacks TbpA/B and LbpA are unable to cause an infection in a human model of gonococcal urethritis. The specific aims of this proposal are 1) to assess the expression of the gonococcal iron-regulated genes by RT-PCR in gonococcal strains acutely obtained from patients with gonococcal infection as an indicator of expression of these proteins, 2) determine the antibody response towards these proteins in patients with mucosal gonococcal disease, 3) determine the specific T cell response towards these proteins in patients with mucosal gonococcal disease and 4) determine if the anti-iron regulated protein immune response can be correlated to prevention of male to female transmission of gonococcal infection.