Neonatal immunity against C. trachomatis infections

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DESCRIPTION (provided by applicant): Of all sexually transmitted bacterial diseases, Chlamydia trachomatis infections are the most common ones in all nations of the world. Most pregnant women infected with C. trachomatis transmit infections to their neonates at birth. Neonatal chlamydial infections include inclusion conjunctivitis and pneumonia. In the U.S., the rate of neonatal infection is 8.2 per 1,000 live births. These infections are associated with a high incidence of morbidity and economic loss, but if diagnosed in time, can be treated with antibiotics. However, the use of antibiotics creates several potential problems, including compliance with medicine regimens, development of persistent infections, emergence of antibiotic- resistant strains, and drug allergies. In addition, antibiotic treatment has been associated with enhanced susceptibility to reinfection at the population level. Therefore, development of a therapeutic vaccine or treatment for neonatal infections may be an effective way to counteract these problems. Because we currently lack an appropriate animal model, knowledge of C. trachomatis infections during the neonatal period is limited. Recently, our laboratory developed a neonatal mouse model of the C. trachomatis infection using the C. trachomatis mouse pneumonitis biovar (MoPn). In this model, newborn pups born to previously MoPn-infected dams are inoculated intranasally at 48 hours of age. Pups then are euthanized at various days post-inoculation to monitor bacterial burden in their lungs. This study's overall aim is to identify a Th1 immune component in mediating a C. trachomatis infection in neonates. More specifically, the research will investigate the role of Th1 immunity in resolving C. trachomatis infections during the neonatal period. This study's hypothesis is that a Th1- mediated immunity is needed to resolve a C. trachomatis infection in neonatal life. To test the hypothesis, newborn pups will receive MoPn-specific T-cells, or Th1-modulating/mediating cytokines, and an intranasal infection will be used to evaluate the efficacy of the adoptive immunity. We predict that neonates with added Th1 immunity will clear C. trachomatis infections more effectively than the non-recipient neonates. The study's result will help us to develop a therapeutic neonatal vaccine against C. trachomatis infections. PUBLIC HEALTH RELEVANCE: Chlamydia trachomatis infections are a major health problem in both developed and underdeveloped countries. The goal of this proposal is to develop a vaccine for the newborn babies who are born from Chlamydia infected mothers. Decreasing the incidence and prevalence of these infections with a vaccine will have a major health impact worldwide.