Discovery and Refinement of Preventive STI Vaccines Targeting Critical Epitopes o

针对关键表位的预防性性病疫苗的发现和改进

• 批准号: 9315698
• 负责人: Bryce C Chackerian
• 金额: $ 30.65万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9315698
• 关键词: Affinity; Animal Model; Antibodies; Antibody Response; Antibody titer measurement; Antigen Presentation; Antigens; Attenuated; Bacteria; Bioinformatics; Biometry; Biotechnology; Capsid Proteins; Cessation of life; Chlamydia trachomatis; Coupled; Diagnosis; Disease; Dose; Engineering; Enterobacteria phage MS2; Epidemiology; Epitopes; Etiology; Formulation; Generations; Genital system; Goals; Grant; Human; Human Papilloma Virus Vaccine; Human Papillomavirus; Immune response; Immune system; Immunity; Immunization; Immunize; Immunologics; Infection; Infectious Agent; Infertility; L2 viral capsid protein; Laboratories; Libraries; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Maps; Methods; Minor; National Institute of Allergy and Infectious Disease; Pathogenicity; Pathway interactions; Pelvic Inflammatory Disease; Peptides; Phage Display; Prevention; Preventive; Program Development; RNA Phages; Sexually Transmitted Diseases; Surface Antigens; System; Techniques; Technology; Testing; Translating; United States National Institutes of Health; Urogenital Cancer; Vaccines; Virus-like particle; acute symptom; base; clinical development; cost; deep sequencing; genital infection; immunogenic; immunogenicity; killings; neutralizing antibody; pathogen; product development; prophylactic; reproductive tract; response; secondary infection; synergism; vaccine candidate; vaccine discovery; virtual

EPIC-STI PROJECT 2 (CHACKERIAN): Discovery and Refinement of Preventive STI Vaccines Targeting Critical Epitopes of Human Papillomaviruses and Chlamydia trachomatis SUMMARY Human Papillomavirus (HPV) and Chlamydia trachomatis (CT) are the two most common sexually transmitted infections (STIs) worldwide. HPV is the etiological agent of virtually all cases of cervical cancer and a large percentage of other cancers of the urogenital tract. Untreated CT infection of the genital tract can cause significant acute symptoms as well as longer term complications, including pelvic inflammatory disease (PID) and infertility. The goal of this project in the Epidemiology and Prevention Interdisciplinary Center (EPIC) for Sexually Transmitted Infections (EPIC-STI) is to develop effective broadly effective vaccines targeting these two important STIs. We have developed a Virus-like Particle (VLP) based peptide display and affinity selection platform. This platform integrates the potent immunogenicity of VLP display with an affinity selection capability that allows the identification of vaccine candidates by two complementary methods. First, we can engineer the VLPs to display specific targets in a highly multivalent format that renders the target potently immunogenic. We have this approach to develop a second generation, broadly neutralizing HPV vaccine that is capable of blocking infection by all of the HPV types associated with cervical cancer, not just the two types targeted by the current vaccine. Second, we can use the VLP platform to identify vaccines from large libraries of potential vaccines by affinity selection using antibodies. In this project, we will use this approach to map epitopes targeted by the natural antibody response to CT infection, with the goal of identifying potential prophylactic CT vaccines. This project will draw heavily of biostatistics and bioinformatics facilities provided by Core B and will have significant synergy with Project 3 (Gravitt) and Project 1 (Starnbach).

EPIC-STI项目2(Chackerian)：预防性STI疫苗靶向的发现和改进 人乳头瘤病毒和沙眼衣原体的关键表位 摘要 人乳头瘤病毒(HPV)和沙眼衣原体(CT)是最常见的两种性传播疾病 全世界的传播感染(STI)。人乳头瘤病毒是几乎所有宫颈癌和 在其他泌尿生殖道癌中占很大比例。未经治疗的生殖道CT感染可导致 严重的急性症状和较长期的并发症，包括盆腔炎 和不孕不育。该项目在流行病学和预防跨学科中心(EPIC)的目标是 性传播感染(EPIC-STI)是针对这些人开发有效、广泛有效的疫苗 两个重要的性传播疾病。 我们开发了一个基于病毒样颗粒(VLP)的多肽展示和亲和力选择平台。这 Platform将VLP显示器强大的免疫原性与亲和力选择能力相结合，使 通过两种互补的方法确定候选疫苗。首先，我们可以将VLP设计成 以高度多价的形式展示特定靶标，使靶标具有强大的免疫原性。我们有 这种开发第二代、广泛中和HPV疫苗的方法能够阻止 感染与宫颈癌相关的所有HPV类型，而不仅仅是当前 疫苗。其次，我们可以使用VLP平台从大型潜在疫苗库中识别疫苗，方法是 使用抗体的亲和力选择。在这个项目中，我们将使用这种方法来映射 对CT感染的天然抗体反应，目的是确定潜在的预防性CT疫苗。这 该项目将大量利用核心B提供的生物统计和生物信息学设施，并将具有重要的 与项目3(Gravitt)和项目1(Starnbach)的协同作用。