Vaccination of dogs with a recombinant cysteine protease from the intestine of canine hookworms diminishes the fecundity and growth of worms
Vaccination of dogs with a recombinant cysteine protease from the intestine of canine hookworms diminishes the fecundity and growth of worms
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DOI：
10.1086/386346
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发表时间：
2004-05-15
影响因子：
6.4
通讯作者：
Hotez, PJ
中科院分区：
文献类型：
--
作者：
Loukas, A;Bethony, JM;Hotez, PJ
我们表达了一种催化活性的半胱氨酸蛋白酶，Ac-CP-2，从犬钩虫犬钩虫的血液喂养阶段，并与纯化的蛋白酶接种疫苗的狗。犬获得了高滴度的抗原特异性抗体应答，从接种犬肠道中回收的钩虫成虫显著小于对照犬的钩虫。接种犬的粪便虫卵计数和雌性钩虫数量也明显减少。Ac-CP-2由寄生虫在其消化道的刷状缘膜中表达，并且抗Ac-CP-2抗体结合到来自接种疫苗的狗的钩虫的肠道，这表明这些抗体被寄生虫与其血餐一起摄取。来自接种疫苗的狗的IgG使针对肽底物的蛋白水解活性降低73%，这意味着通过接种疫苗诱导中和抗体。这些结果表明，参与寄生虫营养的半胱氨酸蛋白酶是有前途的候选人作为疫苗对钩虫病。
We expressed a catalytically active cysteine protease, Ac-CP-2, from the blood-feeding stage of the canine hookworm Ancylostoma caninum and vaccinated dogs with the purified protease. Dogs acquired high-titer, antigen-specific antibody responses, and adult hookworms recovered from the intestines of vaccinated dogs were significantly smaller than hookworms from control dogs. There was also a marked decrease in fecal egg counts and the number of female hookworms in vaccinated dogs. Ac-CP-2 is expressed by the parasite in the brush-border membrane of its alimentary canal, and anti-Ac-CP-2 antibodies were bound to the gut of hookworms from vaccinated dogs, which suggests that these antibodies were ingested by the parasites with their blood meal. IgG from vaccinated dogs decreased proteolytic activity against a peptide substrate by 73%, which implies that neutralizing antibodies were induced by vaccination. These results indicate that cysteine proteases involved in parasite nutrition are promising candidates as vaccines against hookworm disease.