Intranasal vaccination with a secreted chlamydial protein enhances resolution of genital Chlamydia muridarum infection, protects against oviduct pathology, and is highly dependent upon endogenous gamma interferon production
Intranasal vaccination with a secreted chlamydial protein enhances resolution of genital Chlamydia muridarum infection, protects against oviduct pathology, and is highly dependent upon endogenous gamma interferon production
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DOI：
10.1128/iai.01280-06
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发表时间：
2007-02-01
影响因子：
3.1
通讯作者：
Arulanandam, Bernard P.
中科院分区：
文献类型：
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作者：
Murthy, Ashlesh K.;Chambers, James P.;Arulanandam, Bernard P.
目前还没有针对沙眼衣原体的许可疫苗，沙眼衣原体是全球性传播细菌疾病的主要原因。使用表面暴露的衣原体抗原的常规疫苗接种尝试仅取得部分成功。我们采用了一种新型疫苗接种策略，使用分泌蛋白、衣原体蛋白酶样活性因子（CPAF），该因子已被证明可以降解宿主主要组织相容性复合体转录因子和角蛋白-8，因此可能允许免疫逃避和建立生产性感染。采用重组CPAF（rCPAF）+IL-12（rCPAF+IL-12）滴鼻免疫BALB/c小鼠，观察其对小鼠生殖道衣原体感染的保护性免疫。rCPAF+IL-12免疫在体外用rCPAF回忆时诱导脾细胞产生稳健的γ干扰素（IFN-γ）和最小的IL-4产生。与仅接受rCPAF的动物相比，rCPAF+IL-12疫苗接种后血清中的总抗rCPAF抗体和免疫球蛋白G2 a（IgG 2a）抗rCPAF抗体水平显著升高，支气管肺泡灌洗液和阴道液中的总抗体、IgG 2a和伊加水平也显著升高。与模拟免疫（磷酸盐缓冲盐水）的动物相比，rCPAF+IL-12免疫的小鼠在衣原体攻击后表现出显著减少的细菌脱落和加速的感染消退。此外，rCPAF+IL-12免疫的动物表现出对衣原体感染的病理后果的保护，包括输卵管积水和输卵管扩张的发展。在细菌攻击后，将动物与模拟免疫（磷酸盐缓冲盐水）动物进行比较时，该疫苗接种方案还减少了纤维化的发展和中性粒细胞流入上生殖道。rCPAF+IL-12介导的细菌感染的消退和对衣原体诱导的炎性疾病的保护高度依赖于内源性IFN-γ的产生。总之，这些结果表明分泌的衣原体抗原可能是诱导保护性免疫的新型疫苗候选物。
There is currently no licensed vaccine against Chlamydia trachomatis, the leading cause of sexually transmitted bacterial disease worldwide. Conventional vaccination attempts using surface-exposed chlamydial antigens have achieved only partial success. We have employed a novel vaccination strategy using a secreted protein, chlamydial protease-like activity factor (CPAF), which has been shown to degrade host major histocompatibility complex transcription factors and keratin-8 and therefore may allow immune evasion and establishment of a productive infection. Intranasal immunization using recombinant CPAF (rCPAF) plus interleukin-12 (IL-12) (rCPAF+IL-12 immunization) was used to assess the protective immunity against genital Chlamydia muridarum infection in BALB/c mice. rCPAF+IL-12 immunization induced robust gamma interferon (IFN-gamma) production and minimal IL-4 production by splenocytes upon in vitro recall with rCPAF. The total and immunoglobulin G2a (IgG2a) anti-rCPAF antibody levels in serum were significantly elevated after rCPAF+IL-12 vaccination, as were the total antibody, IgG2a, and IgA levels in bronchoalveolar lavage and vaginal fluids when the animals were compared to animals that received rCPAF alone. rCPAF+IL-12-vaccinated mice displayed significantly reduced bacterial shedding upon chlamydial challenge and accelerated resolution of infection compared to mock-immunized (phosphate-buffered saline) animals. Moreover, rCPAF+IL-12-immunized animals exhibited protection against pathological consequences of chlamydial infection, including the development of hydrosalpinx and oviduct dilatation. This vaccination regimen also reduced the development of fibrosis and the influx of neutrophils into the upper genital tract when the animals were compared to mock-immunized (phosphate-bufered saline) animals after bacterial challenge. rCPAF+IL-12-mediated resolution of the bacterial infection and protection against Chlamydia-induced inflammatory disease were highly dependent on endogenous IFN-gamma production. Together, these results demonstrate that secreted chlamydial antigens may be novel vaccine candidates to induce protective immunity.