Bacteriophage virus-like particle vaccines for Chlamydia trachomatis urogenital infection

点击翻译按钮获取中文摘要

PROJECT SUMMARY Chlamydia trachomatis is an obligate intracellular bacteria that is the most common bacterial sexually transmitted infection. Despite effective antibiotic treatment and screening programs, the prevalence of chlamydia continues to rise. Although the infection can be asymptomatic, some women experience serious long-term sequelae, including pelvic inflammatory disease, infertility, and ectopic pregnancy. For these reasons, a prophylactic vaccine against chlamydia is needed. However, significant gaps exist in our knowledge of the natural immune response to urogenital Chlamydia trachomatis infection. In particular, the specificity of antibodies elicited during infection, their functions, and their protective capacity are not well understood. The overall goal of this research is to design prophylactic antibody-eliciting vaccines against urogenital Chlamydia trachomatis infection. The objective of this proposal is to define the range of protective functions antibodies can have against Chlamydia trachomatis infection of the female urogenital tract, and use this knowledge to create vaccines that can elicit those antibodies. Our working hypothesis is that antibody responses that target proteins known to be involved in adhesion and entry into host cells or mediate pathology in the reproductive tract will be protective against urogenital Chlamydia trachomatis infection. In Aim 1, we will engineer epitope-specific vaccine candidates that will elicit high titer antibodies to Chlamydia trachomatis adhesion factors and define their immunogenicity in mouse immunization studies. In Aim 2, we will investigate the specific functions of vaccine-elicited antibodies to neutralize Chlamydia trachomatis infection in cell culture, mediate complement killing of Chlamydia trachomatis, and facilitate uptake and killing by neutrophils. In Aim 3, we will investigate the protective capacity of our vaccines in mouse models of Chlamydia infection. We will investigate the bacterial burden in the upper reproductive tract, bacterial shedding, pathology, and male urogenital tract infection. Overall, these studies will define the role of epitope-specific antibodies in urogenital Chlamydia trachomatis infection and lead to the identification of novel targets for Chlamydia trachomatis vaccine design.