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: 10461735
• 负责人: Anna Wald
• 金额: $ 203.89万
• 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/10461735
• 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.

摘要