IMMUNOCHEMISTRY OF CHLAMYDIAL SURFACE ANTIGENS

这个项目的总体目标是开发一种疫苗来预防

The overall goal of this project is the development of a vaccine to prevent of control blindness and infertility caused by Chlamydia trachomatis. The chlamydial major outer membrane protein (MOMP) is the principle target antigen for the development of a chlamydia vaccine. In past work, we have undertaken extensive studies aimed at defining the antigenic structure of the MOMP at the molecular level. Our objective was to identify structurally and functionally both help-T (TH) and protective B-cell epitopes of the MOMP that we believe to be key antigenic targets for the development of a synthetic or recombinant subunit chlamydial vaccine. From this work we identified an antigenically common TH-cell MOMP epitope, that provides cognate help for the production of neutralizing antibodies targeted serovar and conserved species-specific MOMP B-cell epitopes. Co- linearly synthesized chimeric T:B peptides corresponding to MOMP sequences containing the conserved TH-cell epitope and serovar and species-specific B-cell epitopes induced functional chlamydial neutralizing antibody responses of the desired sero-specificity in strains of congenic mice differing at H-2. The chimeric peptides were also able to prime for neutralizing antibody responses following secondary challenge with sub- immunogenic quantities of intact chlamydiae. These immunogenic properties suggest that the synthetic T:B peptide immunogens my have considerable potential in chlamydial vaccine development. To directly access the utility of the chimeric peptide immunogens as vaccine candidates we studied their immunogenicity and vaccine efficacy in a sub-human primate model of C. trachomatis ocular infection. Cynomolgus monkeys immunized parenterally with the synthetic peptide immunogens produced serum neutralizing antibodies but failed to produce detectable tear antibodies. Vaccinated monkeys were partially protected following ocular challenge with C. trachomatis in that they shed fewer chlamydiae and had significantly less disease. Partial protection was associated with a rapid appearance of neutralizing IgG antibodies in the tears of vaccinated monkeys which was likely localized to the eye by transudation. These findings are the first to demonstrate a beneficial effect of parenteral vaccination against C. trachomatis ocular infection using an antigenically defined immunogen. Future work will focus on combining parenteral and oral immunization protocols to stimulate both mucosal and systemic immunity in attempts to produce a more solid protective immunity.