RECOMBINANT POLYTYPIC CHLAMYDIA VACCINE

重组多型衣原体疫苗

• 批准号: 3140781
• 负责人: LUIS M DE LA MAZA
• 金额: $ 13.45万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-01 至 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3140781
• 关键词: Chlamydia trachomatis; antibody formation; chlamydial disease; genetic manipulation; immunological substance; laboratory mouse; membrane proteins; microorganism antigen; microorganism immunology; trachoma vaccine; transfection; vaccinia virus

The objective of this proposal is to develop a recombinant polytypic vaccine for Chlamydia trachomatis infections. C. trachomatis is one of the most common sexually transmitted pathogens in the Western world and in underdeveloped countries is the etiological agent of trachoma and lymphogranuloma venereum a sever systemic disease. Therefore, an effective vaccine is needed to limit the morbidity and mortality associate with this organism. In this proposal the first step is toe construct a chimeric vaccinia virus vaccine with the gene coding for the major outer membrane protein (MOMP) of the C. trachomatis L3 serovar. Antibodies to this protein have been shown to occur in a majority of Chlamydial infections and furthermore, polyclonal and monoclonal antibodies to the MOMP are known to neutralize Chlamydial infectivity. The MOMP gene will be inserted into a vaccinia virus and the recombinant virus will be tested for expression of MOMP. Mice will be inoculated with the chimeric vaccinia virus-C. trachomatis L3 MOMP vaccine and then they will e challenged with infectious Chlamydiae. The ability of the vaccine to prevent or to modify systemic homotypic and heterotypic Chlamydial infections will be tested. In the case that the C. trachomatis L3 MOMP vaccinia vaccine protects against a challenge with all the C. trachomatis serovars we will subclone the four antigenic variable sequences (VS1, VS2, VS3, and VS4) of the C. trachomatis L3 MOMP into the vaccinia virus and we will test them for their ability to provide protection against a challenge with the 15 C. trachomatis serovars. If on the other hand the C. trachomatis L3 MOMP vaccine proves to have only homotypic or subspecies specificity we will then proceed to isolate and characterize the MOMP genes from the J, E and F serovars and to construct vaccinia virus C. trachomatis chimeras. Thee chimeric vaccines, independently and in combination, will be tested for their ability to protect against infectious homotypic and heterotypic C. trachomatis challenges. We expect that vaccination with the genes from the four serovars will protect the mice against a challenge by any of the 15 C. trachomatis serovars. If this proves to be true, a single vaccinia virus-C. trachomatis chimera vaccine will be constructed which expresses the C. trachomatis MOMP genes from the L3, J, E and F serovars. In the case that we obtain protection with this combined vaccine, and based on the data obtained with the L3 vaccine, we will construct a chimeric vaccinia virus polytypic C. trachomatis vaccine with those variable sequences of the L3, J, E and F serovars that confer protection. This recombinant vaccinia virus-C. trachomatis vaccine will be tested for its ability to protect mice against a systemic challenge with all the C. trachomatis serovars.

这项建议的目的是开发一种重组多型 沙眼衣原体感染疫苗。沙眼衣原体是 在西方世界最常见的性传播病原体和 在不发达国家是沙眼和沙眼的病原体 性淋巴肉芽肿是一种严重的全身性疾病。因此，一个 需要有效的疫苗来限制发病率和死亡率。 与这种生物联系在一起。在这个建议中，第一步是评估 构建编码牛痘病毒基因的嵌合痘苗病毒疫苗 沙眼衣原体L3血清型主要外膜蛋白(MOMP)。 这种蛋白质的抗体已被证明存在于大多数 衣原体感染以及多克隆和单克隆性 抗MOMP的抗体已知能中和衣原体的传染性。 MOMP基因将被插入到痘苗病毒中并重组 将对病毒进行MOMP表达检测。小鼠将接种疫苗 与嵌合痘苗病毒C。沙眼衣原体L3 MOMP疫苗和 然后，他们将受到传染性衣原体的挑战。的能力 预防或改变系统同型和异型的疫苗 将对衣原体感染进行检测。在C. 沙眼衣原体L3MOMP痘苗疫苗预防挑战 我们将对沙眼衣原体的所有血清型进行亚克隆 沙眼衣原体L3的可变序列(VS1、VS2、VS3和VS4) 将MOMP注入痘苗病毒，我们将测试它们是否有能力 为沙眼衣原体的挑战提供保护 血型。另一方面，如果沙眼衣原体L3 MOMP疫苗 证明只有同型或亚种特异性，那么我们就会 继续分离和鉴定J、E和F的MOMP基因 并构建沙眼衣原体病毒嵌合体。你 将对独立和联合使用的嵌合疫苗进行测试 对感染同型和异型C. 沙眼病毒的挑战。我们预计，用来自于 这四个血清型将保护小鼠免受下列任何一个的挑战 沙眼衣原体15个血清型。如果这被证明是真的，一个单一的 牛痘病毒-C。将构建沙眼衣原体嵌合体疫苗， 表达沙眼衣原体L3、J、E、F株MOMP基因 血型。在我们通过这一组合获得保护的情况下 疫苗，根据L3疫苗获得的数据，我们将 构建嵌合痘苗病毒多型沙眼衣原体疫苗 与L3、J、E和F血清型的那些可变序列 保护。重组痘苗病毒C。沙眼衣原体疫苗将 测试其保护小鼠免受系统性挑战的能力 所有的沙眼衣原体血清型。