MOLECULAR CHLAMYDIAL VACCINE DEVELOPMENT

本工作的总体目标是设计和开发一个

The overall objective of this work is the design and development of a synthetic peptide vaccine for the prevention or control of sexually transmitted diseases (STDs) caused by C. trachomatis. Chlamydial STDs are caused by multiple serovars and therefore an efficious vaccine must be capable of evoking a broadly cross protective response that can be targeted to evoke local (mucosal) immunity. The membrane protein (MOMP) is the most promising antigen for the development of a chlamydial vaccine. We have identified and mapped at the molecular level T-helper and B-cell neutralizing epitopes of the MOMP that are antigenically common among those C. trachomatis serovars that are important etiological agents of chlamydial STDs. These key epitopes of the MOMP were co-linearly synthesized as a large chimeric T:B cell oliopeptide and its immunogenenic properties studied in mice and sub-human primates. The oligopepitde immunogen was immunogenic in many congenic mouse strains differing at H-2, and effectively targeted the production of high titered broadly cross- neutralizing anti-chlamydial antibodies. The oligopeptide was also highly immunogenic in sub-human primates evoking a strong heterotypic serum neutralizing antibody response. Parenteral immunization of primates did not produce local neutralizing antibodies and did not confer protection against cervical challenge with chlamydiae. Future work will focus on alternate immunization stratagies with the oligopeptide designed to induce mucosal immunity. These studies will include encapsulation of the oligopeptide into biodegradable/ biocompatable microspheres or liposomes, cross-linking of the peptide to cholera toxin B-subunits, and the construction of recombinant attenuated poliovirus vectors expressing targeted chlamydial neutralizing epitopes.