RECOMBINANT POLYTYPIC CHLAMYDIA VACCINE

重组多型衣原体疫苗

• 批准号: 3140779
• 负责人: LUIS M DE LA MAZA
• 金额: $ 14.31万
• 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/3140779
• 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.

该提案的目的是开发重组多型 沙眼衣原体感染疫苗。 沙眼衣原体是其中之一 西方世界最常见的性传播病原体 在不发达国家，它是沙眼的病原体 性病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 与这个有机体有联系。 在这个提案中，第一步是脚趾 构建具有编码基因的嵌合痘苗病毒疫苗 沙眼衣原体 L3 血清型的主要外膜蛋白 (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感染 已知 MOMP 抗体可以中和衣原体感染性。 MOMP 基因将被插入痘苗病毒中，并重组 将测试病毒的 MOMP 表达。 小鼠将被接种 与嵌合痘苗病毒-C。 沙眼衣原体 L3 MOMP 疫苗和 然后他们将面临传染性衣原体的挑战。 的能力 预防或改变全身同型和异型的疫苗 将测试衣原体感染。 在这种情况下，C. 沙眼衣原体 L3 MOMP 痘苗疫苗可预防以下疾病的挑战 我们将亚克隆所有沙眼衣原体血清型的四种抗原 沙眼衣原体 L3 的可变序列（VS1、VS2、VS3 和 VS4） MOMP 进入痘苗病毒，我们将测试它们的能力 提供针对 15 沙眼衣原体感染的保护 血清型。 另一方面，如果沙眼衣原体 L3 MOMP 疫苗 证明仅具有同型或亚种特异性，然后我们将 继续从 J、E 和 F 中分离和表征 MOMP 基因 血清型并构建痘苗病毒沙眼衣原体嵌合体。 你 将单独和组合地测试嵌合疫苗 它们具有抵御同型和异型传染性的能力 C. 沙眼衣原体挑战。我们期望用来自的基因进行疫苗接种 四种血清型将保护小鼠免受任何挑战 15 种沙眼衣原体血清型。 如果这被证明是正确的，那么一个 痘苗病毒-C.将构建沙眼嵌合疫苗 表达来自 L3、J、E 和 F 的沙眼衣原体 MOMP 基因 血清型。 如果我们通过这种组合获得保护 疫苗，并根据 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 具有 L3、J、E 和 F 血清型的可变序列 保护。 这种重组痘苗病毒-C.沙眼疫苗会 测试其保护小鼠免受全身性挑战的能力 与所有沙眼衣原体血清型。