Department of Microbiology, Immunology and Biochemistry, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Vaccine. 2011 Feb 4;29(7):1472-80. doi: 10.1016/j.vaccine.2010.12.024. Epub 2010 Dec 22.
We tested the hypothesis that intramuscular immunization with a multisubunit chlamydial vaccine candidate will induce long lasting immune responses in mice. Accordingly, groups of female C57BL/6 mice were immunized intramuscularly with Vibrio cholerae ghosts (VCG) expressing the Poring B and polymorphic membrane protein-D proteins of Chlamydia trachomatis or a control antigen. Humoral and cell-mediated immune responses were evaluated following immunization and after live chlamydial infection. Immunization induced an anamnestic response characterized by chlamydial-specific IgG2a and IgA antibodies in sera and vaginal lavage as well as specific genital and splenic T cell responses. The results also revealed that the local mucosal and systemic cellular and humoral immune effectors induced in mice following immunization with the vaccine candidate are long lasting. Vaccinated mice cleared intravaginal challenge with 10(5) chlamydial inclusion forming units within 12 days compared to control mice, which shed up to 2 × 10(3) IFUs at this time point. Moreover, rechallenge of mice 98 days after resolution of the primary infection resulted in the recall and retention of a relatively high frequency of chlamydial-specific Th1 cells and IgG2a in the genital mucosa. These results provide the first evidence that a VCG-based multisubunit chlamydial vaccine is capable of effectively stimulating anamnestic systemic and mucosal immune responses in mice. The data support further vaccine evaluation and testing for induction of long-term protective immunity.
我们测试了这样一个假设，即通过肌肉内免疫接种多亚单位衣原体疫苗候选物将在小鼠中诱导持久的免疫应答。因此，将一组雌性 C57BL/6 小鼠肌肉内免疫接种表达沙眼衣原体的 Porin B 和多态膜蛋白-D 蛋白的霍乱弧菌幽灵（VCG）或对照抗原。在免疫接种后和活衣原体感染后评估体液和细胞介导的免疫应答。免疫接种诱导了特征性的回忆应答，表现为血清和阴道冲洗液中的衣原体特异性 IgG2a 和 IgA 抗体以及特异性生殖器和脾脏 T 细胞应答。结果还表明，疫苗候选物肌肉内免疫接种后在小鼠中诱导的局部粘膜和全身细胞和体液免疫效应物是持久的。与对照组小鼠相比，接种疫苗的小鼠在 12 天内清除了阴道内的 10(5)个包涵体形成单位的挑战，而对照组小鼠在此时点释放了多达 2×10(3)IFU。此外，在原发性感染消退后 98 天再次挑战小鼠，导致回忆和保留相对高频率的衣原体特异性 Th1 细胞和生殖道粘膜中的 IgG2a。这些结果首次提供了证据，证明基于 VCG 的多亚单位衣原体疫苗能够有效地刺激小鼠的回忆性全身和粘膜免疫应答。这些数据支持进一步评估和测试诱导长期保护免疫的疫苗。
