PROTECTIVE IMMUNITY AGAINST SYPHILIS

针对梅毒的保护性免疫力

• 批准号: 6332446
• 负责人: WESLEY C VAN VOORHIS
• 金额: $ 14.65万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6332446
• 关键词: Treponema pallidum; active immunization; bacterial antigens; bacterial genetics; bacterial proteins; bacterial vaccines; cellular immunity; clinical research; cytotoxic T lymphocyte; genetic polymorphism; genetic strain; human tissue; laboratory rabbit; microorganism immunology; mucosal immunity; nucleic acid sequence; syphilis; vaccine development; vector vaccine

Syphilis is a major public health problem in parts of the US and in the developing world. A vaccine to prevent syphilis is urgently needed. Treponema pallidum subsp. Pallidum, the spirochete that causes syphilis, has 12 polymorphic genes that encode proteins with homology to the major sheath protein (msp) of Treponema denticola. In preliminary experiments, immunization with T. p. pallidum. Nichols strain msp-homologue recombinant proteins was partially protective against challenge with T. p. pallidum Nichols strain. The overall goal of this research is to use msp-homologues to develop a protective vaccine against T. p. pallidum infection. The specific aims of this project are the following: 1. Test the ability of immunization with msp- homologues to protect the challenge with T.p. pallidum Nichols strain. This aim will test the hypothesis that immunizing with msp-homologues of T.p. pallidum Nichols strain will lead to protection against challenge with Nichols strain. Immunization using the variable and constant domains will be compared, as will immunization with multiple versus single msp homologues. 2. Determine the heterogeneity of msp-homologue genes in other strains of T.p. pallidum The RFLPs of the4 variable domains of msp- homologue genes are different from strain to strain. In this aim, the variable domains of different strains will be compared by sequence analysis. 3. Test the ability of immunization with msp-homologues to protect from infection with multiple strains of T.p. pallidum. We hypothesize that strain heterogeneity of msp-homologues explain the lack of cross-protection after infection with heterologous strains. The protective capacity of Nichols strain msp-homologues will be compared with heterologous and Nichols strain challenge. As the diversity of msp-homologues among the strains is understood, a multivalent immunization with msp-homologues will be devised to provide protection against challenge with multiple strains. 4. Test alterative vaccine strategies for protection against T.p. pallidum. This aim will test the hypothesis that delivery of msp-homologues via alternative strategies targeting mucosal and CD8/class I immunity will improve protection against challenge with T.p. pallidum. The results of these studies will lead to an understanding of the mechanisms of protective immunity in syphilis and ultimately lead to a vaccination strategy to prevent syphilis.

梅毒是美国部分地区和发展中国家的一个主要公共卫生问题。迫切需要一种预防梅毒的疫苗。梅毒螺旋体亚种。梅毒螺旋体是引起梅毒的螺旋体，具有 12 个多态性基因，编码与齿垢密螺旋体主要鞘蛋白 (msp) 同源的蛋白质。在初步实验中，用 T. p. 进行免疫。苍白球。 Nichols 菌株 msp-同源重组蛋白对 T. p. 的攻击具有部分保护作用。梅毒尼科尔斯菌株。这项研究的总体目标是利用 msp 同源物开发针对 T. p. 的保护性疫苗。梅毒感染。该项目的具体目标如下： 1.测试msp-同系物免疫保护T.p.挑战的能力。梅毒尼科尔斯菌株。这一目标将检验用 T.p. 的 msp 同系物进行免疫的假设。苍白球尼科尔斯菌株将导致针对尼科尔斯菌株的攻击的保护。将比较使用可变结构域和恒定结构域的免疫，以及使用多个与单个msp同源物的免疫。 2.确定其他T.p菌株中msp同源基因的异质性。苍白球菌 msp-同源基因的 4 个可变域的 RFLP 因菌株而异。为此，将通过序列分析比较不同菌株的可变结构域。 3. 测试用 msp 同源物进行免疫以防止多种 T.p. 菌株感染的能力。苍白球。我们假设 msp 同源物的菌株异质性解释了异源菌株感染后交叉保护的缺乏。 Nichols 菌株 msp-同源物的保护能力将与异源菌株和 Nichols 菌株攻击进行比较。由于了解了菌株之间 msp-同源物的多样性，将设计使用 msp-同源物的多价免疫以提供针对多种菌株攻击的保护。 4. 测试针对 T.p. 的替代疫苗策略。苍白球。这一目标将检验以下假设：通过针对粘膜和 CD8/I 类免疫的替代策略递送 msp 同源物将改善针对 T.p 攻击的保护。苍白球。这些研究的结果将有助于了解梅毒的保护性免疫机制，并最终制定预防梅毒的疫苗接种策略。