Successful vaccination of BALB/c mice against human hookworm (Necator americanus):: the immunological phenotype of the protective response
Successful vaccination of BALB/c mice against human hookworm (Necator americanus):: the immunological phenotype of the protective response
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DOI：
10.1016/s0020-7519(02)00248-5
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发表时间：
2003-01-01
影响因子：
4
通讯作者：
Billett, EE
中科院分区：
文献类型：
--
作者：
Girod, N;Brown, A;Billett, EE
在这种美洲钩虫病的小鼠（BALB/c）模型中，通过皮下或经皮途径以14天为间隔连续接种经γ射线照射的美洲钩虫幼虫（每次接种300条），可对美洲钩虫幼虫（300条）的攻击感染产生高水平的保护作用。经皮接种比皮下接种途径显著更有效，在三次免疫后，感染后3天肺部幼虫负荷分别降低了97.8%和89.3%（P < 0.05）。三次接种的小鼠肠道中未发现虫体。两次经皮接种也减少了虫体负荷，肺部减少57%，肠道减少98%；P < 0.05。在接种动物中，与未接种动物相比，感染后的肺部病理变化（主要是出血）大大减轻。在接种小鼠（而非未接种小鼠）中，肥大细胞在皮肤中聚集并脱颗粒。对接种动物皮肤中mRNA的逆转录 - 聚合酶链反应分析表明，白细胞介素 - 4（IL - 4）相对于γ - 干扰素（γ - IFN）的表达增加。用伴刀豆球蛋白A在体外刺激接种小鼠腋窝（皮肤引流）淋巴结的淋巴细胞，其白细胞介素 - 4蛋白分泌增强，白细胞介素 - 4/γ - 干扰素蛋白比值高于未接种动物的淋巴细胞。在接种小鼠中，与未接种动物相比，IgG1和IgG3（针对幼虫排泄/分泌产物）水平大多升高。这些数据表明BALB/c小鼠成功接种预防人类钩虫感染，并提示局部的Th2反应对于预防美洲钩虫病可能很重要。（C）2002年澳大利亚寄生虫学学会。由爱思唯尔科学有限公司出版。保留所有权利。
In this murine (BALB/c) model of necatoriasis, high levels of protection against challenge infection by Necator americanus larvae (n = 300) were afforded by successive vaccinations at 14-day intervals, either subcutaneously or percutaneously, with gamma-irradiated N. americanus larvae (n = 300). Percutaneous vaccination was significantly more effective than the subcutaneous route, with pulmonary larval burdens at 3 days post-infection being reduced by 97.8 vs. 89.3%, respectively, after three immunisations (P < 0.05). No worms were recovered from the intestines of thrice vaccinated mice. Two percutaneous vaccinations also reduced worm burdens, by 57% in the lungs and 98% in the intestines; P < 0.05. In vaccinated animals, lung pathology (mainly haemorrhage) following infection was greatly reduced compared with non-vaccinated animals. In vaccinated mice (but not in non-vaccinated mice) mast cells accumulated in the skin and were degranulated. RT-PCR analyses of mRNAs in the skin of vaccinated animals indicated increased expression of interleukin (IL)-4 relative to gamma-interferon (gamma-IFN). Lymphocytes from the axillary (skin-draining) lymph nodes of vaccinated mice, stimulated in vitro with concanavalin A, exhibited enhanced secretion of IL-4 protein and a higher IL-4/gamma-IFN protein ratio than lymphocytes from non-vaccinated animals. In vaccinated mice, levels of IgG1 and IgG3 (directed against larval excretory/secretory products) were elevated for the most part compared with those in non-vaccinated animals. These data demonstrate the successful vaccination of BALB/c mice against human hookworm infection and suggest that a localised Th2 response may be important for conferring protection against necatoriasis. (C) 2002 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved.