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: 10219123
• 负责人: CAROLINE E CAMERON
• 金额: $ 34.67万
• 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/10219123
• 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 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.

项目摘要/摘要 引起梅毒的细菌，梅毒螺旋体亚种。梅毒，广泛传播于 被感染的宿主感染每一个器官和组织。之前在卡梅伦实验室进行的研究已经 鉴定了一种暴露在表面的梅毒螺旋体粘附素，命名为Tp0751，它介导与 因此，内皮细胞在梅毒螺旋体的传播过程中起着重要作用。在首字母中 研究表明，用这种梅毒螺旋体粘附素免疫兔子产生的免疫反应提供了 对梅毒螺旋体传播的显著保护。本文件所载研究的长期目标 提案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， 充分保护免疫动物免受传播的梅毒螺旋体感染。为了实现这一目标， 具体目标如下：(1)确定Tp0751免疫原的保护区(S)； 优化Tp0751疫苗原配方；(3)优化Tp0751疫苗原投放；(4)试验 优化的Tp0751和Tpr的异种保护能力和实现保护的持续时间 疫苗配方和投放系统。我们预计这些调查将产生梅毒疑似病例 疫苗表现出对传播性感染的保护，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。