University of Washington (UW) Sexually Transmitted Infections (STI) Cooperative Research Center (CRC) - Syphilis Vaccine to Protect against Local and Disseminated T. pallidum Infection

华盛顿大学 (UW) 性传播感染 (STI) 合作研究中心 (CRC) - 梅毒疫苗可预防局部和播散性梅毒螺旋体感染

• 批准号: 9982766
• 负责人: Anna Wald
• 金额: $ 209.02万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9982766
• 关键词: Adjuvant; Animal Model; Animals; Antibody Response; Antigens; Award; B-Lymphocytes; Basic Science; Biopsy; Blood - brain barrier anatomy; Blood Circulation; Clinic; Clinical; Clinical Trials; Communicable Diseases; Congenital Syphilis; Development; Disease; Endothelium; Epitope Mapping; Epitopes; Failure; Formulation; Fred Hutchinson Cancer Research Center; Genomics; Globus Pallidus; Goals; Grant; Human; Human papillomavirus HPV L1 protein; Immune response; Immunity; Immunization; Immunization Programs; Immunologist; Incidence; Infection; Investigation; Laboratories; Leadership; Lesion; Measures; Mediating; Membrane Proteins; Mentors; Modeling; Mucous Membrane; Mus; Neurosyphilis; Oryctolagus cuniculus; Patients; Penicillins; Persons; Phase; Play; Positioning Attribute; Predisposition; Preventive vaccine; Program Research Project Grants; Protein Family; Proteins; Public Health; Recombinant Proteins; Research; Research Personnel; Research Project Grants; Role; Sampling; Sanitation; Sexually Transmitted Diseases; Skin; Surface; Surface Antigens; Syphilis; Syphilitic chancre; T cell response; T-Lymphocyte; Testing; Training; Translational Research; Treponema pallidum; United States; Universities; Vaccinated; Vaccine Adjuvant; Vaccine Antigen; Vaccines; Vertical Disease Transmission; Viral; Washington; base; clinical infrastructure; combat; design; experience; immunogenicity; improved; member; men who have sex with men; novel strategies; particle; pre-clinical; preclinical study; prevent; recruit; response; syphilis vaccine; vaccine candidate; vaccine development; vaccine trial

ABSTRACT The overarching goal of this Sexually Transmitted Infection Cooperative Research Center (STI CRC) proposal is to develop a candidate vaccine that provides significant protection against T. pallidum infection, the agent that causes syphilis. Despite susceptibility to penicillin, syphilis remains a public health threat worldwide, with an estimated 11 million new infections per year and a global burden of 36 million infections. In the last decade, there has been a resurgence of syphilis, with near doubling of rates among men who have sex with men and rates of congenital syphilis, resulting from mother to child transmission. As such, an effective prophylactic vaccine is required for control in addition to standard public health measures. The University of Washington has a long tradition of outstanding syphilis research: the research team assembled for this proposal has developed preclinical vaccine candidates that have substantial protection in the rabbit model. We propose three inter-related Scientific Projects. In Project 1, we will further refine the T. pallidum Tp0751 protein, which is essential for spread of T. pallidum through the bloodstream, for use as a vaccinogen by optimizing the protein formulation and the mode of delivery of this vaccinogen. In Project 2, we will optimize the TprK, and TprC/D2 proteins for vaccine use, as in animal models immunity to these antigens prevents chancre formation; optimization of these proteins will encompass protective epitope identification as well as optimal delivery of these epitopes. Subsequently, we will test the combined protective capacity of a vaccine cocktail comprised of these proteins in the syphilis rabbit model. In Project 3, we examine the B and T cell responses raised against the Tp0751 and Tpr vaccinogens in natural infection in humans and in vaccinated animals. As adjuvants that evoke immunity in rabbits differ from human-use adjuvants, we will also test the candidate vaccine adjuvanted with human track adjuvants in mouse immunogenicity studies as a prelude to human trials. The Scientific Projects will be supported by three Cores comprised of the Administrative Core, the Clinical and Statistical Core, and the Genomics and Isolation Core; the Developmental Research Project Program will provide mentoring and training to outstanding new investigators in the STI research field. By the end of the 5 year grant timeframe we propose to have a candidate vaccine that is ready for human trials.

抽象的 这个性传播感染合作研究中心（STI CRC）的总体目标 提案是开发一种候选疫苗，可为pallidum感染提供重大保护， 引起梅毒的药物。尽管对青霉素敏感，梅毒仍然是公共卫生威胁 在全球范围内，估计每年有1100万种新感染，全球3600万感染。 在过去的十年中，梅毒已经复兴，男性的比率几乎增加了一倍 与男性发生性关系和先天性梅毒的发生率，从母亲到儿童传播。因此，一个 除了标准公共卫生措施外，还需要有效的预防性疫苗。 华盛顿大学拥有杰出梅毒研究的悠久传统：研究团队 为此提案组装的已经开发了临床前疫苗的候选者 兔子模型。我们提出了三个相互关联的科学项目。在项目1中，我们将进一步完善T。 Pallidum tp0751蛋白，对于通过血液传播的T. pallidum至关重要 通过优化蛋白质制剂和该疫苗的递送方式，疫苗。在项目2中 我们将优化TPRK和用于疫苗使用的TPRC/D2蛋白，如动物模型中的免疫力 抗原可防止chancre形成；这些蛋白质的优化将包含保护性表位 识别以及这些表位的最佳输送。随后，我们将测试合并的 梅毒兔模型中由这些蛋白质组成的疫苗鸡尾酒的保护能力。在项目中 3，我们检查了针对天然中TP0751和TPR疫苗的B和T细胞响应 人类和接种动物的感染。由于兔子免疫的佐剂不同于 人使用佐剂，我们还将测试与人类轨道佐剂佐剂佐剂的候选疫苗 小鼠免疫原性研究是人类试验的前奏。 科学项目将由由行政核心组成的三个核心支持，即临床 和统计核心，以及基因组学和隔离核心；发展研究项目计划 将为STI研究领域的杰出新调查人员提供指导和培训。到结束 我们提议的5年赠款时间范围是为人类试验准备的候选疫苗。