Scanning Chlamydia proteome for vaccine antigens

DESCRIPTION (provided by applicant): Throughout the world Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen. In areas with poor sanitary conditions C. trachomatis causes trachoma the most common cause of preventable blindness in the world. A majority of the genital C. trachomatis infections in women are asymptomatic. In addition, in symptomatic cases, unless therapy is implemented in a timely manner, long-term sequelae including, pelvic inflammatory disease, chronic abdominal pain, ectopic pregnancy and infertility, may develop. Children get infected at the time of birth and can develop conjunctivitis and pneumonia. Thus, the only practical approach to prevent these diseases is vaccinating the population at risk. Here we are going to utilize a high throughput approach to identify new potential candidate antigens for the formulation of a vaccine against C. trachomatis infections. The hypothesis we want to test is that antigens that can induce antibodies can protect against infection, and/or the long-term sequelae of a C. trachomatis infection, e.g., infertility. Using a new approach, developed by ImmPORT Therapeutics, Inc., we are going to clone and express all the proteins from C. trachomatis mouse pneumonitis (MoPn). The expressed proteins will be spotted onto a microarray chip. Three strains of mice will be vaccinated with live and UV-inactivated C. trachomatis MoPn using several mucosal and systemic routes of immunization. The animals will then be challenged intravaginally with C. trachomatis MoPn. To determine the severity and length of the genital infection vaginal cultures will be collected. Six weeks after the intravaginal challenge the mice will be euthanized and their genital tract examined for the presence of scar tissue and hydroxalpinx. Serum samples will be collected on a regular basis from the immunized and intravaginally challenged mice. These serum samples will be profiled based on the presence of antibodies to specific Chlamydia proteins using the microarray chip. Data will be analyzed to reveal any correlation between immune responses against specific subset of antigens and protection profile or disease state. Those proteins that are identified using the microarray chip, as potential vaccine antigens, will be subsequently tested in the phase II of the study for their ability to protect against a genital challenge. An efficacious vaccine against C. trachomatis will have a tremendous sanitary and economic impact throughout the world.