Richter D, Incani R N, Harn D A
Department of Tropical Public Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Infect Immun. 1996 May;64(5):1826-31. doi: 10.1128/iai.64.5.1826-1831.1996.
Carbohydrates on soluble egg antigens are major epitopes for the antibody responses of patients and mice infected with Schistosoma mansoni. Recently, protective sera of mice vaccinated with irradiated cercariae were shown to recognize carbohydrate epitopes on schistosomal glutathione S-transferase. The present study demonstrates that carbohydrate epitopes are major targets of sera from C57BL/6J and CBA/J mice vaccinated with 15- or 50-kilorad-irradiated cercariae of S. mansoni. Antibody titers to carbohydrate epitopes increased with the number of vaccinations and were considerably higher in C57BL/6J mice than in CBA/J mice. The specificity of this anticarbohydrate response was determined by measuring antibody binding to defined oligosaccharide residues known to be present on the parasite. A predominant target of the humoral anticarbohydrate response of vaccinated mice was lacto-N-fucopentaose III, a molecule relevant for cell trafficking. We observed no binding to its nonfucosylated homolog, lacto-N-neotetraose, or to oligosaccharides present on keyhole limpet hemocyanin. The strongest antibody response to lacto-N-fucopentaose III was observed for C57BL/6J and CBA/J mice repeatedly vaccinated with 15-kilorad-irradiated cercariae, which also achieve the highest levels of protection. Immunoglobulin M was the predominant antibody class binding to lacto-N-fucopentaose III. We conclude that in the irradiated-cercariae vaccine model, C57BL/6J and CBA/J mice produce anticarbohydrate antibodies against various stages of S. mansoni and that the oligosaccharide lacto-N-fucopentaose III is one target of this response. Lacto-N-fucopentaose III and its specific antibodies may profoundly affect host resistance and parasite homing.
可溶性虫卵抗原上的碳水化合物是感染曼氏血吸虫的患者和小鼠抗体反应的主要表位。最近,用辐照尾蚴免疫的小鼠的保护性血清显示可识别血吸虫谷胱甘肽S-转移酶上的碳水化合物表位。本研究表明,碳水化合物表位是用15或50千拉德辐照的曼氏血吸虫尾蚴免疫的C57BL/6J和CBA/J小鼠血清的主要靶标。针对碳水化合物表位的抗体滴度随免疫次数增加而升高,且C57BL/6J小鼠中的抗体滴度显著高于CBA/J小鼠。通过测量抗体与已知存在于寄生虫上的特定寡糖残基的结合来确定这种抗碳水化合物反应的特异性。免疫小鼠体液抗碳水化合物反应的主要靶标是乳糖-N-岩藻戊糖III,一种与细胞运输相关的分子。我们未观察到其与非岩藻糖基化同系物乳糖-N-新四糖或与钥孔血蓝蛋白上存在的寡糖的结合。对于用15千拉德辐照尾蚴反复免疫的C57BL/6J和CBA/J小鼠,观察到对乳糖-N-岩藻戊糖III的最强抗体反应,这些小鼠也实现了最高水平的保护。免疫球蛋白M是与乳糖-N-岩藻戊糖III结合的主要抗体类别。我们得出结论,在辐照尾蚴疫苗模型中,C57BL/6J和CBA/J小鼠产生针对曼氏血吸虫各个阶段的抗碳水化合物抗体,且寡糖乳糖-N-岩藻戊糖III是该反应的一个靶标。乳糖-N-岩藻戊糖III及其特异性抗体可能深刻影响宿主抗性和寄生虫归巢。