Bacteriophage virus-like particle vaccines for Chlamydia trachomatis urogenital infection

用于沙眼衣原体泌尿生殖感染的噬菌体病毒样颗粒疫苗

• 批准号: 10584334
• 负责人: Kathryn M. Frietze
• 金额: $ 38.31万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-06 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10584334
• 关键词: Adhesions; Animal Model; Antibiotic Therapy; Antibodies; Antibody Response; Antibody Specificity; Antibody titer measurement; Antibody-mediated protection; Antigens; Automobile Driving; Bacteria; Bacteriophages; Binding; CD4 Positive T Lymphocytes; Cell Culture Techniques; Cells; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Complement; Data; Ectopic Pregnancy; Engineering; Epitopes; Female; Genitourinary System Infection; Genitourinary system; Goals; Human; Immune; Immune Sera; Immune response; Immunity; Immunization; Immunize; In Vitro; Infection; Infertility; Interferon Type II; Knowledge; Licensing; Mediating; Mucous Membrane; Mus; Nature; Oryctolagus cuniculus; Passive Transfer of Immunity; Pathology; Pelvic Inflammatory Disease; Peptides; Phagocytes; Prevalence; Preventive vaccine; Proteins; Publishing; Recording of previous events; Research; Role; Safety; Sexually Transmitted Diseases; T cell response; T-Lymphocyte; Test Result; Testing; United States National Institutes of Health; Vaccine Design; Vaccines; Virus-like particle; Woman; Work; antibody test; chlamydia vaccine; design; effective therapy; experience; immunogenic; immunogenicity; in vitro Assay; in vivo; innovation; interest; long-term sequelae; major outer membrane protein; male; mouse model; neutrophil; novel; novel strategies; prophylactic; reproductive tract; response; screening program; treatment program; tubal infertility; uptake; urogenital tract; vaccine access; vaccine candidate; vaccine development; vaccine platform; vaccine strategy

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.

项目总结 沙眼衣原体是一种专性胞内细菌，是最常见的性传播细菌。 感染。尽管有效的抗生素治疗和筛查计划，衣原体的流行仍在继续 站起来。尽管感染可能没有症状，但一些女性会经历严重的长期后遗症， 包括盆腔炎、不孕症和异位妊娠。出于这些原因，一种避孕药 需要针对衣原体的疫苗。然而，在我们对自然免疫的认识上存在着显著的差距。 对泌尿生殖道沙眼衣原体感染的反应。特别是，在此过程中产生的抗体的特异性 感染、它们的功能以及它们的保护能力还不是很清楚。这项研究的总体目标 目的是设计预防沙眼衣原体感染的抗体疫苗。这个 这项提案的目的是确定抗体对衣原体具有的保护功能的范围 沙眼衣原体感染女性生殖道，并利用这一知识创造疫苗，可以诱导 那些抗体。我们的工作假设是，抗体的反应是针对已知涉及的蛋白质 在生殖道中黏附和进入宿主细胞或中介病理将保护免受 泌尿生殖道沙眼衣原体感染。在目标1中，我们将设计出表位特异的候选疫苗 将诱导沙眼衣原体黏附因子高滴度抗体并确定其免疫原性 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定功能 在细胞培养中中和沙眼衣原体感染，介导沙眼衣原体补体杀伤， 并促进中性粒细胞的摄取和杀伤。在目标3中，我们将调查我们的疫苗的保护能力 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、病理和男性泌尿生殖道感染。总体而言，这些研究将确定 泌尿生殖道沙眼衣原体感染的表位特异性抗体及其新基因的鉴定 沙眼衣原体疫苗设计的目标。