Production and characterization of anti-idiotypic antibodies, biological mimicry of a glycolipid exoantigen of Chlamydia trachomatis in vivo
Abstract (Summary)Irrespective of the fact that chlamydial infections afflict more than 500 millions of people in the world, little is known about host defense mechanisms involved. Several chlamydial antigens are being investigated in an effort to find a vaccine candidate. The dilemmas currently confronted in searching for a vaccine are answers to the following questions: (1) How are the chlamydial antigens recognized by the immune system without resolving the infection? (2) What epitopes, if any (natural, synthetic) can be used as a vaccine? (3) What is the mechanism of immune responses involved in the neutralization of the infection in vivo? The work presented here has approached the above fundamental issues by studies on anti-idiotypic antibodies which biologically mimic a genus specific chlamydial glycolipid exoantigen (GLXA). The monoclonal idiotypic antibody (mAb$\sb1$), specific to GLXA, was used in the production of xenogeneic anti-idiotypic antibodies (Ab$\sb2$) and syngeneic anti-idiotypic antibodies (mAb$\sb2$) in guinea pigs and BALB/cByJ mice respectively. The internal image of GLXA has been screened and confirmed. The neutralization of ocular infection by rabbit Ab$\sb3$ was demonstrated in a primate trachoma model. The primates who received C. trachomatis elementary bodies pretreated with Ab$\sb3$ IgG had a 78% reduction in infected eyes compared to those infected with organisms pretreated with pre-immune IgG. Almost none chlamydial ribosomal RNA detected in those primate conjunctivae, as opposed to controls, suggests that the neutralization by Ab$\sb3$ occurred at very early stage of infection. MAb$\sb2$ as an immunogen elicits a strong immunity to C. trachomatis in a syngeneic mouse infection model. One hundred percent ocular infection occurred in mice immunized with normal mouse IgG compared to 12.5% of mouse eyes immunized with mAb$\sb2$ on day 21 after infection. Immunologic memory was demonstrated in the protected mice by immunity upon rechallenge. This study for the first time demonstrates that anti-idiotypic antibodies which mimic a chlamydial antigen protects animal models from ocular infection, revealing that the antigen, GLXA is essential in initiating the chlamydial infection. The conversion of a saccharide epitope to a protein (immunoglobulin) epitope may have transformed the thymus-independent immune response to a thymus-dependent immune response, thus evoking a protective host defense mechanism.
School Location:USA - Massachusetts
Source Type:Master's Thesis
Date of Publication:01/01/1993