Discovery of Treponema pallidum antigens for development of a sensitive and specific diagnostic test for syphilis

发现梅毒螺旋体抗原，用于开发敏感且特异的梅毒诊断测试

• 批准号: 9906085
• 负责人: Joseph J Campo
• 金额: $ 30万
• 依托单位: IMMPORT THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9906085
• 关键词: Address; Affect; Amino Acid Sequence; Antibodies; Antigens; Appearance; Bacteria; Binding; Binding Proteins; Biological Assay; Biological Markers; Blindness; Cardiovascular system; Cells; Clinical; Collaborations; Communities; Complex; Core Protein; Country; Data; Detection; Developed Countries; Developing Countries; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Progression; Early Diagnosis; Fetal Mortality Statistics; Fluorescence; Future; Genes; Genetic; Genetic Transcription; Genome; Genomics; Globus Pallidus; Goals; HIV; Human; Immunoglobulin G; Immunoglobulin M; In Vitro; Income; Individual; Infection; Inflammatory; Kinetics; Knowledge; Laboratories; Lead; Maternal-Fetal Transmission; Measures; Modeling; Modernization; Monitor; Morbidity - disease rate; Nature; Neonatal Mortality; Neurologic; Order Spirochaetales; Oryctolagus cuniculus; Patients; Peru; Peruvian; Phase; Population; Pregnant Women; Prevalence; Protein Array; Proteins; Proteome; Proteomics; Public Health; Pyroxylin; Relapse; Research; Research Personnel; Sampling; Sensitivity and Specificity; Serologic tests; Serological; Serum; Slide; Small Business Innovation Research Grant; Specificity; Staging; Stroke; Syphilis; Syphilis Serodiagnosis; Technology; Testing; Translations; Treponema pallidum; Universities; Variant; Vertical Disease Transmission; Washington; base; co-infection; deafness; diagnostic assay; diagnostic biomarker; epidemiology study; global health; high risk; high risk population; improved; innovation; low and middle-income countries; men who have sex with men; novel; novel diagnostics; novel marker; prevent; prototype; sample collection; stem; stillbirth; success; tool; transgender women; transmission process; treatment response; validation studies

In spite of being perceived as a disease of the past, syphilis remains a serious global health problem, affecting millions worldwide in both developing and developed countries. In underprivileged setting, syphilis is a significant cause of stillbirth and neonatal mortality due to vertical transmission during pregnancy, while in developed countries, it affects particularly high risk groups such as men who have sex with men (MSM). If untreated, syphilis often results in serious neurological and cardiovascular complications, including blindness, deafness, stroke and aortic aneurism. A better and simpler diagnostic test is desired to replace the current two-assay diagnostic tests, especially if early diagnosis and disease staging can be distinguished. A practical proteome-scale platform for antibody profiling has never before been available to the syphilis research community, and this technology has the power to rapidly discovery novel biomarkers and improve syphilis diagnostics approaches. Antigen Discovery, Inc. (ADI) of Irvine, CA, will develop a Treponema pallidum subspecies pallidum (TP) panproteome microarray to measure specific anti-TP IgG and IgM antibody levels in longitudinally collected sera from rabbits experimentally infected with syphilis agents and in patient sera. To this end, ADI will partner with two established syphilis investigators, Dr. Lorenzo Giacani, based at the University of Washington and expert in the use of the rabbit model of syphilis, and Dr. Jeffrey Klausner, based at UCLA, renowned for his syphilis epidemiological studies in MSM and transgender women in Lima, Peru.The panproteome array will include up to 1,000 syphilis proteins representing two groups of modern syphilis strains currently circulating globally. We hypothesize that certain anti-TP antibodies can serve as biomarkers to detect early infections or repeat infections, as well as different disease stages. The most promising diagnostic candidates will be identified in the rabbit model, which has exquisite control over the timing of sample collection after infection, treatment and reinfection. Subsequently, the top candidates will be confirmed in humans by testing the sera from Peruvian patients with varying stages of disease. We expect to identify several TP proteins that are recognized by antibodies, some which appear soon after infection and some that correlate with the stage of disease. Future studies will validate diagnostic markers and develop a prototype diagnostic test that can be tested for FDA 510(k) clearance. This application addresses the necessity of simplifying and improving syphilis diagnostics approaches, and choses to do it through the application of an innovative proteomic technology mastered by ADI. If successful, our endeavor will provide new tools and knowledge to help stem the spread of this serious infection.

尽管被视为过去的疾病，但梅毒仍然是一个严重的全球健康问题，影响 在发展中国家和发达国家，全球数百万。在贫困的环境中，梅毒是重要的 由于怀孕期间垂直传播而导致死产和新生儿死亡率的原因，而发达 国家，它影响了特别高风险群体，例如与男性发生性关系的男性（MSM）。如果未经治疗，梅毒 通常会导致严重的神经系统和心血管并发症，包括失明，耳聋，中风和 主动脉动脉瘤。需要更好，更简单的诊断测试来替换当前的两场诊断测试， 特别是如果可以区分早期诊断和疾病分期。一个实用的蛋白质组规模平台 梅毒研究界从未有过抗体分析，这项技术已经 快速发现新型生物标志物并改善梅毒诊断方法的力量。抗原 加利福尼亚州欧文市的Discovery，Inc。（ADI）将开发treponema Pallidum subpecies Pallidum（TP）Panploteome 微阵列在纵向收集的兔子血清中测量特定的抗TP IgG和IgM抗体水平 通过梅毒剂和患者血清中的实验感染。为此，ADI将与两个已建立的合作 梅毒研究人员，洛伦佐·吉亚卡尼（Lorenzo Giacani）博士，位于华盛顿大学 梅毒的兔子模型和位于加州大学洛杉矶分校的杰弗里·克劳斯纳博士以其梅毒流行病学而闻名 秘鲁利马的MSM和变性妇女的研究。 代表两组现代梅毒菌株的蛋白质目前在全球循环。我们假设这一点 某些抗TP抗体可以用作检测早期感染或重复感染的生物标志物以及 不同的疾病阶段。最有希望的诊断候选人将在兔子模型中确定 对感染，治疗和重新感染后的样本收集时间进行精致的控制。随后， 人类将通过测试秘鲁患者的血清，该阶段的阶段不同 疾病。我们希望识别几种抗体识别的TP蛋白，有些很快出现 感染后，有些与疾病阶段相关。未来的研究将验证诊断标记 并开发一个原型诊断测试，可以对FDA 510（k）清除进行测试。此应用程序地址 简化和改善梅毒诊断方法的必要性，并选择通过 ADI掌握的创新蛋白质组学技术的应用。如果成功，我们的努力将提供新的 工具和知识有助于阻止这种严重感染的传播。