RECOMBINANT POLYTYPIC CHLAMYDIA VACCINE

重组多型衣原体疫苗

• 批准号: 3140782
• 负责人: LUIS M DE LA MAZA
• 金额: $ 13.98万
• 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 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3140782
• 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.

本提案的目的是开发一种重组多型 沙眼衣原体感染的疫苗。 C.沙眼是一种 西方世界最常见的性传播病原体， 在不发达国家是沙眼的病原体， 性病性淋巴肉芽肿是一种严重的全身性疾病。 所以一间 需要有效的疫苗来限制发病率和死亡率 与这种有机体有关。 在这个提案中，第一步是脚趾 构建具有编码以下的基因的嵌合牛痘病毒疫苗： 主要外膜蛋白（MOMP）。沙眼衣原体L3血清型 这种蛋白质的抗体已被证明出现在大多数 衣原体感染，此外，多克隆和单克隆 已知MOMP的抗体可中和衣原体感染性。 将MOMP基因插入牛痘病毒中， 将检测病毒的MOMP表达。 小鼠将接种 嵌合痘苗病毒-C。 沙眼L3 MOMP疫苗和 然后用传染性衣原体进行攻击 的能力 预防或改变系统性同型和异型的疫苗 将检测衣原体感染。 在C. 沙眼衣原体L3 MOMP牛痘疫苗可保护免受 所有的C。沙眼衣原体血清型，我们将亚克隆四种抗原 可变序列（VS1，VS2，VS3和VS4）的C.沙眼衣原体L3 MOMP进入牛痘病毒，我们将测试他们的能力， 提供针对15 C挑战的保护。沙眼衣原体 血清型 另一方面，C.沙眼L3 MOMP疫苗 证明只有同型或亚种特异性，我们将 继续分离和表征来自J、E和F的MOMP基因 血清型，构建C型痘苗病毒。沙眼嵌合体 你 嵌合疫苗，独立和组合，将测试 它们对感染性同型和异型C的保护能力。 沙眼挑战我们希望接种来自 这四种血清型将保护小鼠免受任何 15 C.沙眼血清型 如果这是真的，一个 牛痘病毒C.将构建沙眼嵌合体疫苗， 表达了C.来自L3、J、E和F的沙眼衣原体MOMP基因 血清型 在这种情况下，我们获得保护与此相结合 根据L3疫苗获得的数据， 构建嵌合多型C型痘苗病毒。沙眼疫苗 与L3、J、E和F血清型的那些可变序列， 保护 该重组痘苗病毒-C。沙眼疫苗将 测试其保护小鼠免受系统性攻击的能力 所有的C。沙眼血清型