Tsuji Naotoshi, Miyoshi Takeharu, Islam M Khyrul, Isobe Takashi, Yoshihara Shinobu, Arakawa Takeshi, Matsumoto Yasunobu, Yokomizo Yuichi
National Institute of Animal Health, National Agricultural Research Organization, Tsukuba, Ibaraki, Japan.
J Infect Dis. 2004 Nov 15;190(10):1812-20. doi: 10.1086/425074. Epub 2004 Sep 30.
We recently cloned a protective antigen that is commonly expressed in Ascaris species that infect humans and pigs. We evaluated the vaccinal effects of this 16-kilodalton protein (As16) in pigs, the natural host of Ascaris suum, by intranasal immunization. Pigs that received Escherichia coli-expressed recombinant As16 (rAs16) coupled with cholera toxin (CT) had significantly elevated levels of rAs16-specific serum immunoglobulin G (IgG) and mucosal-associated IgA antibodies. rAs16 evoked a type II immune response characterized by elevated levels of interleukin-4 and -10 in the culture supernatants of peripheral blood mononuclear cells of the vaccinated pigs. An increased level of rAs16-specific serum IgG1 was also detected. Pigs vaccinated with rAs16-CT were protected from migration of A. suum larvae through the lungs, as indicated by a 58% reduction in the recovery of lung-stage third-stage larvae (L3), compared with that in nonvaccinated controls. Purified immunoglobulin from rAs16-CT-vaccinated pigs inhibited survival of infective L3 and interrupted the molting of lung-stage L3. Immunofluorescence studies revealed that this immunoglobulin bound to the digestive tracts of L3, suggesting that it might inactivate functions of the gut tissues of Ascaris species. We conclude that rAs16 is a promising mucosal vaccine candidate for pig and human ascariasis.
我们最近克隆了一种保护性抗原,该抗原在感染人类和猪的蛔虫物种中普遍表达。我们通过鼻内免疫评估了这种16千道尔顿蛋白(As16)在猪(猪蛔虫的天然宿主)中的疫苗效果。接受大肠杆菌表达的重组As16(rAs16)与霍乱毒素(CT)结合的猪,其rAs16特异性血清免疫球蛋白G(IgG)和黏膜相关IgA抗体水平显著升高。rAs16引发了II型免疫反应,其特征是接种疫苗猪的外周血单个核细胞培养上清液中白细胞介素-4和-10水平升高。还检测到rAs16特异性血清IgG1水平增加。与未接种疫苗的对照组相比,接种rAs16-CT的猪可免受猪蛔虫幼虫通过肺部的迁移,肺阶段三期幼虫(L3)的回收率降低了58%,这表明了这一点。来自接种rAs16-CT猪的纯化免疫球蛋白抑制了感染性L3的存活,并中断了肺阶段L3的蜕皮。免疫荧光研究表明,这种免疫球蛋白与L3的消化道结合,表明它可能使蛔虫物种的肠道组织功能失活。我们得出结论,rAs16是一种有前途的用于猪和人类蛔虫病的黏膜疫苗候选物。