A combination of antigenic regions of Toxoplasma gondii microneme proteins induces protective immunity against oral infection with parasite cysts

A combination of antigenic regions of Toxoplasma gondii microneme proteins induces protective immunity against oral infection with parasite cysts
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DOI:
10.1086/427660
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发表时间:
2005-02-15
影响因子:
6.4
通讯作者:
Gargano, N
Gargano, N
中科院分区:
医学2区
文献类型:
--
作者:
Beghetto, E;Nielsen, HV;Gargano, N

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弓形虫感染导致先天性感染和免疫功能低下个体的发病率和死亡率。体液和细胞介导的免疫都参与了宿主对寄生虫入侵的抵抗。在假定的候选疫苗中,T.弓形虫微线蛋白似乎是有希望的,因为它们负责入侵过程。目前的工作重点是研究感染个体和慢性弓形虫病小鼠模型中微线体蛋白的免疫原性。我们在MIC2、MIC4、MIC2相关蛋白和顶膜抗原1基因产物中鉴定了5个不同的抗原区域,这些区域被(1)获得性感染成人和先天性感染儿童的T细胞和(2)所有患者的抗体识别。最后,我们证明了微线片段的DNA免疫在小鼠中引起了有效的保护(脑囊肿负荷减少84%),这表明在设计抗弓形虫病的潜在疫苗时应考虑这些抗原区域的组合。
Infection with Toxoplasma gondii causes morbidity and mortality in congenitally infected and immunocompromised individuals. Both humoral and cell-mediated immunity are involved in host resistance to invasion of the parasite. Among putative vaccine candidates, the T. gondii microneme proteins appear to be promising, because they are responsible for the invasion process. The present work focused on studying the immunogenicity of microneme proteins in infected individuals and in a mouse model of chronic toxoplasmosis. We identified 5 distinct antigenic regions within MIC2, MIC4, MIC2-associated protein, and apical membrane antigen 1 gene products, which were recognized by ( 1) T cells from both adults with acquired infection and children with congenital infection and ( 2) antibodies from all patients. Finally, we demonstrated that DNA immunization with microneme fragments elicited effective protection in mice (84% reduction in brain-cyst burden), suggesting that a combination of these antigenic regions should be considered in the design of potential vaccines against toxoplasmosis.