A novel recombinant multisubunit vaccine against Chlamydia
A novel recombinant multisubunit vaccine against Chlamydia
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DOI：
10.4049/jimmunol.173.5.3375
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发表时间：
2004-09-01
影响因子：
4.4
通讯作者：
Igietseme, JU
中科院分区：
文献类型：
--
作者：
Eko, FO;He, Q;Igietseme, JU
接种有效的疫苗是控制沙眼衣原体引起的人类眼生殖器感染的最有效的长期措施。衣原体基因组测序已经确定了许多潜在的候选疫苗，目前的挑战是开发一种有效的运载工具，用于诱导高水平的粘膜T和互补B细胞应答。霍乱弧菌血影（VCG）是一种无毒、有效的载体，具有很强的佐剂性质，能够在粘膜组织中诱导T细胞和Ab应答。我们调查的假设，rVCG可以作为一个或多个亚单位衣原体疫苗，以诱导高水平的保护性免疫有效的运载工具。表达rVCG的衣原体外膜蛋白通过两步遗传过程产生，包括在霍乱弧菌中克隆Omp基因，然后进行基因E介导的细胞裂解。比较表达rVCG单亚基和多亚基的疫苗的免疫原性和疫苗效力。免疫学分析表明，i.m.用任一种疫苗构建体免疫小鼠诱导了针对整个衣原体生物体的强粘膜和全身特异性Th1应答。然而，与单亚单位构建体相比，多亚单位疫苗诱导更高频率的Th1细胞和相对更大的赋予保护性免疫的能力具有免疫原性优势。这些结果支持了操作理论，即疫苗赋予针对衣原体的保护性免疫的能力是引发的Th1应答水平的函数。
The administration of an efficacious vaccine is the most effective long-term measure to control the oculogenital infections caused by Chlamydia trachomatis in humans. Chlamydia genome sequencing has identified a number of potential vaccine candidates, and the current challenge is to develop an effective delivery vehicle for induction of a high level of mucosal T and complementary B cell responses. Vibrio cholerae ghosts (VCG) are nontoxic, effective delivery vehicles with potent adjuvant properties, and are capable of inducing both T cell and Ab responses in mucosal tissues. We investigated the hypothesis that rVCG could serve as effective delivery vehicles for single or multiple subunit chlamydial vaccines to induce a high level of protective immunity. rVCG-expressing chlamydial outer membrane proteins were produced by a two-step genetic process, involving cloning of Omp genes in V. cholerae, followed by gene E-mediated lysis of the cells. The immunogenicity and vaccine efficacy of rVCG-expressing single and multiple subunits were compared. Immunologic analysis indicated that i.m. immunization of mice with either vaccine construct induced a strong mucosal and systemic specific Th1 response against the whole chlamydial organism. However, there was an immunogenic advantage associated with the multiple subunit vaccine that induced a higher frequency of Th1 cells and a relatively greater ability to confer protective immunity, compared with the single subunit construct. These results support the operational theory that the ability of a vaccine to confer protective immunity against Chlamydia is a function of the level of Th1 response elicited.