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首页> 外文期刊>Infection and immunity >Nucleic Acid Vaccination with Schistosoma mansoni Antioxidant Enzyme Cytosolic Superoxide Dismutase and the Structural Protein Filamin Confers Protection against the Adult Worm Stage
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Nucleic Acid Vaccination with Schistosoma mansoni Antioxidant Enzyme Cytosolic Superoxide Dismutase and the Structural Protein Filamin Confers Protection against the Adult Worm Stage

机译：曼氏血吸虫抗氧化酶的胞浆超氧化物歧化酶和结构蛋白菲拉明的核酸疫苗赋予了针对成虫阶段的保护作用

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Schistosomiasis remains a worldwide endemic cause of chronic and debilitating illness. There are two paradigms that exist in schistosome immunology. The first is that the schistosomule stages are the most susceptible to immune killing, and the second is that the adult stage, through evolution of defense mechanisms, can survive in the hostile host environment. One mechanism that seems to aid the adult worm in evading immune killing is the expression of antioxidant enzymes to neutralize the effects of reactive oxygen and nitrogen species. Here, we challenge one paradigm by targeting adult Schistosoma mansoni worms for immune elimination in an experimental mouse model using two S. mansoni antioxidants, cytosolic superoxide dismutase (SmCT-SOD) and glutathione peroxidase (SmGPX), and a partial coding sequence for a structural protein, filamin, as DNA vaccine candidates. DNA vaccination with SmCT-SOD induced a mean of 39% protection, filamin induced a mean of 50% protection, and SmGPX induced no protection compared to controls following challenge with adult worms by surgical transfer. B- and T-cell responses were analyzed in an attempt to define the protective immune mechanism(s) involved in adult worm killing. SmCT-SOD-immunized mice presented with a T1 response, and filamin-immunized mice showed a mixed T1-T2 response. We provide evidence for natural boosting after vaccination. Our results demonstrate that adult worms can be targeted for immune elimination through vaccination. This represents an advance in schistosome vaccinology and allows for the development of a therapeutic as well as a prophylactic vaccine.
机译：血吸虫病仍然是世界范围内慢性病和衰弱性疾病的流行病。血吸虫免疫学存在两种范式。首先是血吸虫阶段最容易受到免疫杀伤，其次是成年阶段，通过防御机制的演变，可以在敌对宿主环境中生存。似乎有助于成虫蠕虫逃避免疫杀伤的一种机制是抗氧化剂酶的表达，以中和活性氧和氮物种的影响。在这里，我们通过针对成年的曼氏血吸虫蠕虫针对使用两种 S的实验小鼠模型进行免疫消除来挑战一种范例。 Mansoni抗氧化剂，胞质超氧化物歧化酶（SmCT-SOD）和谷胱甘肽过氧化物酶（SmGPX）以及结构蛋白丝质蛋白的部分编码序列作为DNA疫苗候选物。与成虫通过手术转移攻击相比，用SmCT-SOD进行的DNA疫苗接种平均可实现39％的保护，丝质蛋白平均可实现50％的保护，而SmGPX则无保护。分析了B细胞和T细胞反应，以试图确定与杀灭成年蠕虫有关的保护性免疫机制。 SmCT-SOD免疫小鼠表现出T1应答，而丝素蛋白免疫小鼠表现出混合的T1-T2应答。我们提供疫苗接种后自然加强的证据。我们的结果表明，成虫可以通过疫苗接种来消除免疫。这代表了血吸虫病疫苗学的进步，并允许开发治疗性和预防性疫苗。

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