PROTECTIVE IMMUNITY AGAINST 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一种引起梅毒的螺旋体，它有12个多态基因，编码与齿密螺旋体主鞘蛋白(MSP)同源的蛋白质。在初步实验中，用梅毒螺旋体免疫。Nichols株MSP同源重组蛋白对梅毒螺旋体Nichols株的攻击有部分保护作用。这项研究的总体目标是利用MSP同源物开发一种针对梅毒螺旋体感染的保护性疫苗。本课题的具体目标如下：1.检测MSP同源物免疫对T.P.攻击的保护能力。梅毒螺旋体尼科尔斯菌株。这一目的将检验用T.P.的MSP同源物免疫的假设。梅毒螺旋体尼科尔斯株可抵抗尼科尔斯株的攻击。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MSP同源物和单一MSP同源物的免疫。2.确定T.P.其他菌株MSP同源基因的异质性。梅毒MSP同源基因的4个可变区的RFLP在不同菌株之间是不同的。为此，将通过序列分析来比较不同毒株的可变区。3.检测MSP同源物免疫小鼠对多株弓形虫的保护作用。梅毒。我们假设，MSP-同源物的菌株异质性解释了感染异源菌株后缺乏交叉保护的原因。将Nichols株MSP-同源物的保护能力与异源株和Nichols株的攻击能力进行比较。由于了解了菌株间MSP同源物的多样性，将设计一种使用MSP同源物的多价免疫，以提供保护免受多个菌株的挑战。4.测试预防T.P.的替代疫苗策略。梅毒。这一目标将检验这样一种假设，即通过针对粘膜和CD8/I类免疫的替代策略传递MSP同源物将改善对T.P攻击的保护。梅毒。这些研究的结果将有助于理解梅毒的保护性免疫机制，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.