Eko Francis O, He Qing, Brown Teresa, McMillan Lucinda, Ifere Godwin O, Ananaba Godwin A, Lyn Deborah, Lubitz Werner, Kellar Kathryn L, Black Carolyn M, Igietseme Joseph U
Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
J Immunol. 2004 Sep 1;173(5):3375-82. doi: 10.4049/jimmunol.173.5.3375.
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.
接种有效的疫苗是控制人类沙眼衣原体引起的眼生殖系统感染的最有效长期措施。衣原体基因组测序已鉴定出一些潜在的疫苗候选物，当前的挑战是开发一种有效的递送载体，以诱导高水平的黏膜T细胞和互补B细胞反应。霍乱弧菌幽灵（VCG）是无毒的有效递送载体，具有强大的佐剂特性，能够在黏膜组织中诱导T细胞和抗体反应。我们研究了rVCG能否作为单一或多个亚单位衣原体疫苗的有效递送载体，以诱导高水平的保护性免疫这一假设。表达衣原体外膜蛋白的rVCG通过两步基因工程方法制备，包括将Omp基因克隆到霍乱弧菌中，随后通过基因E介导细胞裂解。比较了表达单一和多个亚单位的rVCG的免疫原性和疫苗效力。免疫分析表明，用任一疫苗构建体对小鼠进行肌肉注射免疫均能诱导针对整个衣原体生物体的强烈黏膜和全身特异性Th1反应。然而，与单一亚单位构建体相比，多个亚单位疫苗具有免疫原性优势，可诱导更高频率的Th1细胞，并具有相对更强的赋予保护性免疫的能力。这些结果支持了一种操作理论，即疫苗赋予针对衣原体的保护性免疫的能力是所引发的Th1反应水平的函数。
