Bacteriophage virus-like particle vaccines for Chlamydia trachomatis urogenital infection

项目摘要 沙眼衣原体是一种专性细胞内细菌，是最常见的细菌性传播 感染尽管有有效的抗生素治疗和筛查计划，衣原体的流行仍在继续 上升。虽然感染可能没有症状，但有些妇女会出现严重的长期后遗症， 包括盆腔炎、不孕症和宫外孕。出于这些原因， 需要针对衣原体的疫苗。然而，我们对天然免疫系统的认识存在重大差距。 泌尿生殖道沙眼衣原体感染的反应。特别是，在免疫过程中引发的抗体的特异性 感染、它们的功能和它们的保护能力还不很清楚。本研究的总体目标是 目的是设计针对泌尿生殖道沙眼衣原体感染的预防性抗体诱导疫苗。的 本提案的目的是确定抗体对衣原体的保护功能范围 沙眼感染的女性泌尿生殖道，并利用这一知识，创造疫苗， 这些抗体。我们的工作假设是，针对已知参与的蛋白质的抗体反应 在粘附和进入宿主细胞或介导的病理在生殖道将保护， 泌尿生殖道沙眼衣原体感染在目标1中，我们将设计表位特异性疫苗候选物， 将引发针对沙眼衣原体粘附因子的高滴度抗体， 小鼠免疫研究。在目标2中，我们将研究疫苗诱导的抗体的特异性功能， 中和细胞培养物中的沙眼衣原体感染，介导沙眼衣原体的补体杀伤， 并促进嗜中性粒细胞的摄取和杀伤。在目标3中，我们将研究疫苗的保护能力 在衣原体感染的小鼠模型中。我们将调查上生殖道的细菌负荷， 细菌脱落、病理学和男性泌尿生殖道感染。总的来说，这些研究将确定以下方面的作用： 表位特异性抗体在泌尿生殖道沙眼衣原体感染中的作用， 沙眼衣原体疫苗设计的目标。

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.