Studies of human immune responses to various antigenic proteins of Chlamydia trachomatis

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Chlamydiae are gram-negative bacteria which cause diverse diseases of humans and animals. Chlamydia trachomatis, the focus of this work, causes the blinding eye disease trachoma, and reproductive tract infections. Trachoma affects 500 million individuals of whom seven million are blind. Chlamydia is the most common reproductive tract infection and can cause pelvic inflammatory disease and tubal infertility. In both cases treatment with antibiotics is effective but they may not be available, recurrent infection is common and the long-terrn complications irreversible. A vaccine is needed but attempts at developing one have met with limited success. The recent discovery of a family of antigenic surface proteins, the polymorphic membrane proteins, has revitalised the search for potential vaccine candidates. One member of this family, pmpG, was cloned in two fragments and the recombinant products expressed and purified. Humoral and cellular responses to these and other chlamydial antigens, and to common recall antigens, were examined in human subjects in The Gambia using immunoblotting, whole blood assay and cytokine ELISA techniques. Children with active trachoma, adults with trachomatous scarring and women with tubal infertility were examined, together with matched controls. PmPG was shown to be a target of both humoral and cellular responses. These responses were more commonly directed towards the amino- (PmpGa), rather than carboxylterminal (PmpGc) fragment. Antibodies to PmPGa were associated with a reduced risk of active trachoma but antibodies to PmpGc were associated with conjunctival scarring. PmPGa stimulated the production of TNFa, IFNy and TGFb. Children with active trachoma produced higher levels of TNFa and IL-10 than controls in response to PmPGa. High levels of IL-10 in response to both chlamydial and common recall antigens were noted in children with active trachoma and this may be a mechanism by which Chlamydia survives intracellularly. Responses to other chlarnydial proteins were characterised and an association between intestinal helminth infection and conjunctival scarring was noted.