Intranasal immunization with gal-inhibitable lectin plus an adjuvant of CpG oligodeoxynucleotides protects against Entamoeba histolytica challenge
Intranasal immunization with gal-inhibitable lectin plus an adjuvant of CpG oligodeoxynucleotides protects against Entamoeba histolytica challenge
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DOI：
10.1128/iai.00725-07
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发表时间：
2007-10-01
影响因子：
3.1
通讯作者：
Chadee, Kris
中科院分区：
文献类型：
--
作者：
Ivory, Catherine P. A.;Chadee, Kris
开发一种有效的阿米巴病疫苗可以改善发展中国家的儿童健康，减少阿米巴结肠炎和肝脓肿的病例。一种理想的疫苗应该由一种特性良好的寄生虫抗原和一种佐剂组成，这种佐剂将具有高效力，同时将免疫反应驱动到Th1方向。本研究描述了一种由溶组织内阿米巴凝集素(Gal-galactose/N-acetyl-D-galactosamine-inhibitable)和CpGODN组成的黏膜疫苗。半乳糖凝集素是一种参与寄生虫毒力和黏附的蛋白质，已知可以激活免疫细胞，而CpG-ODN是已知的I型免疫反应的有效诱导者。我们证明，鼻腔注射疫苗会导致强烈的半乳糖凝集素特异性Th1反应和体液反应。疫苗接种诱导了半乳糖凝集素特异性T细胞的产生和促炎细胞因子γ干扰素的产生。免疫动物在体外可检测到血清抗半乳糖凝集素免疫球蛋白G(Ig G)和粪便抗半乳糖凝集素IgA能阻断寄生虫与靶细胞的黏附。免疫后一周，用活滋养体肝内攻击沙土鼠。接种疫苗的沙土鼠在第5天后没有检测到脓肿，而对照组沙土鼠出现了更大的脓肿。这些结果表明，半乳糖凝集素和CpG-ODN黏膜免疫均能诱导机体产生全身和体液免疫应答。
The development of an effective amebiasis vaccine could improve child health in the developing world, reducing cases of amebic colitis and liver abscess. An ideal vaccine would be comprised of a well-characterized parasite antigen and an adjuvant, which would have high potency while driving the immune response in a Th1 direction. This study describes a mucosal vaccine composed of the Entamoeba histolytica galactose/N-acetyl-D-galactosamine-inhibitable lectin (Gal-lectin) and CpG oligodeoxynucleotides (CpG-ODN). The Gal-lectin is a protein involved in parasite virulence and adherence and is known to activate immune cells, while CpG-ODN are known to be potent inducers of type I-like immune responses. We demonstrated that intranasal administration of the vaccine resulted in strong Gal-lectin-specific Th1 responses and humoral responses. Vaccination induced the production of Gal-lectin-specific T cells and the production of the proinflammatory cytokine gamma interferon. Vaccinated animals had detectable serum anti-Gal-lectin immunoglobulin G (IgG) and stool anti-Gal-lectin IgA capable of blocking parasite adherence to target cells in vitro. One week after immunization, gerbils were challenged intrahepatically with live trophozoites. Vaccinated gerbils had no detectable abscesses after day 5, whereas control gerbils developed larger abscesses. These results show that mucosal vaccination with Gal-lectin and CpG-ODN can induce both systemic and humoral immune responses.