Optimization to Improve the Protective Capacity of the Tp0751 Syphilis Vaccine Candidate

优化提高 Tp0751 梅毒候选疫苗的保护能力

• 批准号: 10461739
• 负责人: CAROLINE E CAMERON
• 金额: $ 34.69万
• 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/10461739
• 关键词: Animals; Antibodies; Antigens; B-Lymphocytes; Bacteria; Bacterial Adhesins; Binding; Biological Assay; Blocking Antibodies; Blood Vessels; Cell Communication; Country; Crystallization; Development; Disease; Endothelial Cells; Endothelium; Escherichia coli; Exhibits; Formulation; Generations; Globus Pallidus; Goals; Haemophilus influenzae; Immune response; Immunity; Immunization; Immunize; Immunoglobulin G; Income; Infection; Investigation; Laboratories; Laminin Receptor; Liposomes; Measurement; Mediating; Modeling; Molecular; Neisseria meningitidis; Organ; Oryctolagus cuniculus; Pathogenicity; Play; Population; Prevalence; Preventive vaccine; Primary Infection; Process; Public Health; Receptor Cell; Research; Role; Sexually Transmitted Diseases; Site; Streptococcus pneumoniae; Surface; Syphilis; System; Testing; Tissues; Treponema pallidum; Universities; Vaccines; Virulent; Washington; clinical investigation; dimer; improved; in vitro testing; in vivo; inhibiting antibody; low and middle-income countries; monomer; pathogen; pre-clinical; prevent; scale up; syphilis vaccine; vaccine candidate; vaccine delivery; vaccine development; vaccine formulation; vaccine trial

PROJECT SUMMARY/ABSTRACT The bacterium that causes syphilis, Treponema pallidum subsp. pallidum, disseminates widely throughout an infected host to infect every organ and tissue. Previous studies conducted in the Cameron laboratory have identified a surface-exposed T. pallidum adhesin, designated Tp0751, which mediates attachment to endothelial cells and, as such, plays an important role in the process of T. pallidum dissemination. In initial studies, immunization of rabbits with this treponemal adhesin induced an immune response that provided significant protection against T. pallidum dissemination. The long-term objective of the studies contained in this proposal is to expand on these prior promising protection results and develop an enhanced vaccinogen that fully protects immunized animals against disseminated T. pallidum infection. To accomplish this objective, the following specific aims are proposed: (1) determine the protective region(s) of the Tp0751 immunogen; (2) optimize the Tp0751 vaccinogen formulation; (3) optimize the delivery of the Tp0751 vaccinogen; and (4) test the heterologous protective capacity and duration of achieved protection of the optimal Tp0751 and Tpr vaccine formulation and delivery system. We anticipate these investigations will generate a syphilis candidate vaccine that exhibits protection against disseminated infection and, when combined with the optimized Tpr vaccinogen from Scientific Project 2, will provide complete protection against syphilis.

项目总结/摘要 引起梅毒的细菌，梅毒螺旋体亚种。苍白球，广泛分布在整个 感染宿主的每一个器官和组织。先前在卡梅隆实验室进行的研究 发现了一个表面暴露的T.苍白球粘附素，命名为Tp 0751，其介导与 因此，在T.苍白球播散初始 研究中，用这种密螺旋体粘附素免疫兔子诱导免疫应答， 对T.苍白球播散本报告所载研究的长期目标是： 一项建议是在这些先前有希望的保护结果的基础上进行扩展，并开发一种增强的疫苗原， 完全保护免疫动物免受播散性T.苍白球感染为了实现这一目标， 提出了以下具体目标：（1）确定Tp 0751免疫原的保护区;（2） 优化Tp 0751疫苗原制剂;（3）优化Tp 0751疫苗原的递送;以及（4）测试 最佳Tp 0751和Tpr的异源保护能力和所实现的保护的持续时间 疫苗制剂和递送系统。我们预计这些调查将产生一个梅毒候选人 显示出针对播散性感染的保护作用的疫苗，并且当与优化的Tpr结合时， 来自科学项目2的疫苗原将提供对梅毒的完全保护。