Induction of immune memory by a multisubunit chlamydial vaccine

Induction of immune memory by a multisubunit chlamydial vaccine
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DOI:
10.1016/j.vaccine.2010.12.024
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发表时间:
2011-02-04
期刊:
影响因子:
5.5
通讯作者:
Igietseme, J. U.
Igietseme, J. U.
中科院分区:
医学3区
文献类型:
--
作者:
Eko, F. O.;Ekong, E.;Igietseme, J. U.

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我们检验了以下假设:用多亚单位衣原体候选疫苗肌肉内免疫将在小鼠中诱导持久的免疫应答。相应地,用表达沙眼衣原体的孔B和多态性膜蛋白-D蛋白的霍乱弧菌血影(VCG)或对照抗原肌内免疫雌性C57 BL/6小鼠组。体液和细胞介导的免疫反应进行了评价免疫接种后,活衣原体感染。免疫诱导的回忆反应,其特征在于衣原体特异性IgG 2a和伊加抗体在血清和阴道灌洗液以及特定的生殖器和脾脏T细胞反应。结果还显示,用候选疫苗免疫后在小鼠中诱导的局部粘膜和全身细胞和体液免疫效应是持久的。与对照组小鼠相比,接种疫苗的小鼠在12天内清除了10(5)个衣原体包涵体形成单位的阴道内攻毒,在该时间点,对照组小鼠脱落了2 x 10(3)个IFU。此外,98天后的决议的主要感染导致的召回和保留的衣原体特异性的Th 1细胞和IgG 2a在生殖器粘膜中的频率相对较高的小鼠的再挑战。这些结果提供了第一个证据表明,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的疫苗评价和检测,以诱导长期保护性免疫。(C)2010爱思唯尔有限公司保留所有权利。
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 x 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. (C) 2010 Elsevier Ltd. All rights reserved.