Cross-reactivity of Schistosoma mansoni cytosolic superoxide dismutase, a protective vaccine candidate, with host superoxide dismutase and identification of parasite-specific B epitopes
Cross-reactivity of Schistosoma mansoni cytosolic superoxide dismutase, a protective vaccine candidate, with host superoxide dismutase and identification of parasite-specific B epitopes
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DOI：
10.1128/iai.72.5.2635-2647.2004
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发表时间：
2004-05-01
影响因子：
3.1
通讯作者：
LoVerde, PT
中科院分区：
文献类型：
--
作者：
Carvalho-Queiroz, C;Cook, R;LoVerde, PT
曼氏血吸虫（Schistosoma mansoni）是一种血管内寄生虫，它已经进化出许多免疫逃避机制来在宿主体内建立自己，如抗氧化酶。我们的实验室已经证明，某些抗氧化酶的最高水平是在蠕虫中发现的，成虫对免疫杀伤最不敏感。与对照组相比，用含有编码Cu/Zn胞质超氧化物歧化酶（SmCT-SOD）的基因的裸DNA构建体接种小鼠显示出显著的保护水平，并且我们的数据表明，蠕虫是赋予SmCT-SOD DNA接种小鼠抗性的免疫应答的靶点。由于SmCT-SOD与人类同源物具有显著的同一性，因此我们评估了来自SmCT-SOD免疫小鼠和兔以及来自S.用人超氧化物歧化酶（hSOD）和SmCT-SOD寄生虫特异性肽对曼氏感染个体进行免疫，以评估用重组分子免疫产生自身免疫应答的潜力。此外，我们还评估了各种SmCT-SOD澄清剂递送的免疫接种诱导交叉反应性抗体的能力。针对SmCT-SOD产生的小鼠和兔抗体均识别变性形式的hSOD。相同的抗体不识别非变性hSOD。不同临床形式的血吸虫病感染者的血清识别SmCT-SOD，但不识别hSOD。来自用不同的含有DNA和蛋白质的SmCT-SOD的制剂免疫的小鼠的抗体能够识别SmCT-SOD衍生的肽，但不能识别可溶性hSOD。总之，这些发现为开发抗血吸虫病亚单位疫苗奠定了基础。
Schistosoma mansoni, an intravascular parasite, has evolved a number of immune evasion mechanisms to establish itself in the host, such as antioxidant enzymes. Our laboratory has demonstrated that the highest levels of certain antioxidant enzymes are found in adult worms, which are the least susceptible to immune killing. Vaccination of mice with naked DNA constructs containing the gene encoding Cu/Zn cytosolic superoxide dismutase (SmCT-SOD) showed significant levels of protection compared to a control group, and our data demonstrate that the adult worms are a target of the immune response that confers resistance in SmCT-SOD DNA-vaccinated mice. Because SmCT-SOD shows significant identity with the human homologue, we evaluated the reactivity of anti-SmCT-SOD antibodies derived from SmCT-SOD-immunized mice and rabbits and from S. mansoni-infected individuals to human superoxide dismutase (hSOD) and SmCT-SOD parasite-specific peptides to assess the potential for autoimmune responses from immunization with the recombinant molecule. In addition, we evaluated the ability of various SmCT-SOD adjuvant-delivered immunizations to induce cross-reactive antibodies. Both mouse and rabbit antibodies generated against SmCT-SOD recognized the denatured form of hSOD. The same antibodies did not recognize nondenatured hSOD. Sera from infected individuals with different clinical forms of schistosomiasis recognized SmCT-SOD but not hSOD. Antibodies from mice immunized with different SmCT-SOD-containing formulations of both DNA and protein were able to recognize SmCT- SOD -derived peptides but not soluble hSOD. All together, these findings serve as a basis for developing a subunit vaccine against schistosomiasis.