PROTECTIVE IMMUNITY AGAINST SYPHILIS

在美国部分地区和发展中国家，梅毒是一个主要的公共卫生问题。迫切需要预防梅毒的疫苗。梅毒螺旋体梅毒螺旋体（Pallidum）是引起梅毒的螺旋体，它有12个多态性基因，编码的蛋白质与齿垢密螺旋体的主鞘蛋白（MSP）具有同源性。在初步实验中，用T.苍白树Nichols菌株msp同源重组蛋白对T. pallidum Nichols菌株。本研究的总体目标是利用msp同源物开发针对T.梅毒螺旋体感染。该项目的具体目标如下：1。测试用msp同源物免疫以保护用T. p. pallidum Nichols菌株攻击的能力。该目的将检验以下假设：用梅毒螺旋体Nichols菌株的msp同源物免疫将导致针对Nichols菌株攻击的保护。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.梅毒螺旋体其它菌株中msp同源基因异质性的测定不同菌株msp同源基因的4个可变区的RFLP各不相同。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同源物免疫以保护免受多种梅毒螺旋体菌株感染的能力。我们推测，菌株的异质性的msp同源物解释缺乏交叉保护感染后与异源菌株。将Nichols菌株msp同源物的保护能力与异源和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，将设计用msp同源物进行多价免疫以提供针对多种菌株攻击的保护。4.测试针对梅毒螺旋体的替代疫苗策略。这一目的将检验这样的假设，即通过靶向粘膜和CD 8/I类免疫的替代策略递送msp同源物将改善对梅毒螺旋体攻击的保护。这些研究的结果将导致对梅毒保护性免疫机制的理解，并最终导致预防梅毒的疫苗接种策略。

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.