Nucleic acid vaccination with Schistosoma mansoni antioxidant enzyme cytosolic superoxide dismutase and the structural protein filamin confers protection against the adult worm stage
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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DOI：
10.1128/iai.72.10.6112-6124.2004
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发表时间：
2004-10-01
影响因子：
3.1
通讯作者：
LoVerde, PT
中科院分区：
文献类型：
--
作者：
Cook, RM;Carvalho-Queiroz, C;LoVerde, PT
血吸虫病仍然是一种世界性的慢性和使人衰弱的疾病的地方病。有两种范式存在于复杂的免疫学中。第一个原因是，幼虫期最容易受到免疫杀伤，第二个原因是，成虫期通过防御机制的进化，可以在敌对的宿主环境中生存。一种似乎有助于成虫逃避免疫杀伤的机制是抗氧化酶的表达，以中和活性氧和氮的影响。在这里，我们挑战一个范例，针对成人曼氏血吸虫蠕虫的免疫消除实验小鼠模型，使用两个S。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），以及结构蛋白细丝蛋白的部分编码序列，作为DNA疫苗候选物。DNA疫苗接种SmCT-SOD诱导的平均39%的保护，细丝蛋白诱导的平均50%的保护，和SmGPX诱导没有保护相比，控制挑战与蠕虫通过手术转移。分析了B细胞和T细胞应答，试图确定成虫杀灭中涉及的保护性免疫机制。SmCT-SOD免疫小鼠呈现T1应答，细丝蛋白免疫小鼠呈现T1-T2混合应答。我们提供了疫苗接种后自然加强的证据。我们的研究结果表明，蠕虫可以通过接种疫苗进行免疫消除。这代表了单克隆抗体疫苗学的进步，并允许开发治疗性和预防性疫苗。
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 schistosomulle 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, cytosollic 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.