Transcutaneous immunization with combined cholera toxin and CpG adjuvant protects against Chlamydia muridarum genital tract infection
Transcutaneous immunization with combined cholera toxin and CpG adjuvant protects against Chlamydia muridarum genital tract infection
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DOI：
10.1128/iai.72.2.1019-1028.2004
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发表时间：
2004-02-01
影响因子：
3.1
通讯作者：
Beagley, KW
中科院分区：
文献类型：
--
作者：
Berry, LJ;Hickey, DK;Beagley, KW
沙眼衣原体是生殖道和眼上皮的病原体。感染是通过代谢惰性初等体（EB）与上皮细胞结合而建立的。它们被内吞作用吸收到称为包涵体的膜结合囊泡中。包涵体避免了与宿主溶酶体的融合，并且EBs分化为代谢活跃的网状体（RB），在包涵体的保护环境中通过二元裂变进行复制。在沙眼衣原体生命周期的细胞外EB期，存在于生殖道或眼分泌物中的抗体在体内和组织培养中都能抑制感染。RB位于细胞内包涵体内，抗体无法接近，在此阶段，感染的解决需要由分泌γ干扰素的Th1细胞介导的细胞介导的免疫反应。因此，一种理想的预防沙眼原体生殖道感染的疫苗应该在粘膜分泌物中诱导抗体（免疫球蛋白A [IgA]和IgG）反应以防止衣原体EB感染，并诱导强烈的Th1反应以限制上升感染到子宫和输卵管。在本研究中，我们发现用主要外膜蛋白（MOMP）联合霍乱毒素和CpG寡脱氧核苷酸经皮免疫，在阴道和子宫灌洗液中引起MOMP特异性IgG和IgA，在血清中引起MOMP特异性IgG，在生殖道引流尾侧和腰椎淋巴结中引起分泌γ干扰素的T细胞。该免疫方案在阴道内攻击BALB/c小鼠后，增强了对沙眼衣原体（沙眼衣原体，小鼠肺炎菌株）的清除。
Chlamydia trachomatis is a pathogen of the genital tract and ocular epithelium. Infection is established by the binding of the metabolically inert elementary body (EB) to epithelial cells. These are taken up by endocytosis into a membrane-bound vesicle termed an inclusion. The inclusion avoids fusion with host lysosomes, and the EBs differentiate into the metabolically active reticulate body (RB), which replicates by binary fission within the protected environment of the inclusion. During the extracellular EB stage of the C. trachomatis life cycle, antibody present in genital tract or ocular secretions can inhibit infection both in vivo and in tissue culture. The RB, residing within the intracellular inclusion, is not accessible to antibody, and resolution of infection at this stage requires a cell-mediated immune response mediated by gamma interferon-secreting Th1 cells. Thus, an ideal vaccine to protect against C trachomatis genital tract infection should induce both antibody (immunoglobulin A [IgA] and IgG) responses in mucosal secretions to prevent infection by chlamydial EB and a strong Th1 response to limit ascending infection to the uterus and fallopian tubes. In the present study we show that transcutaneous immunization with major outer membrane protein (MOMP) in combination with both cholera toxin and CpG oligodeoxynucleotides elicits MOMP-specific IgG and IgA in vaginal and uterine lavage fluid, MOMP-specific IgG in serum, and gamma interferon-secreting T cells in reproductive tract-draining caudal and lumbar lymph nodes. This immunization protocol resulted in enhanced clearance of C. muridarum (C. trachomatis, mouse pneumonitis strain) following intravaginal challenge of BALB/c mice.