Studies of human immune responses to various antigenic proteins of Chlamydia trachomatis
Felton, John Mark;
(2003)
Studies of human immune responses to various antigenic proteins of Chlamydia trachomatis.
PhD thesis, London School of Hygiene & Tropical Medicine.
DOI: https://doi.org/10.17037/PUBS.00682233
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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.