Sm-p80-based DNA vaccine formulation induces potent protective immunity against Schistosoma mansoni.

Sm-p80-based DNA vaccine formulation induces potent protective immunity against Schistosoma mansoni.
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DOI:
10.1111/j.1365-3024.2008.01091.x
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发表时间:
2009-03
影响因子:
2.2
通讯作者:
Siddiqui AA
Siddiqui AA
中科院分区:
医学4区
文献类型:
--
作者:
Ahmad G;Torben W;Zhang W;Wyatt M;Siddiqui AA

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尽管已有治疗血吸虫病的有效药物(吡喹酮),但该病仍然有增无减,在76个国家猖獗。迄今为止,通过吡喹酮治疗进行控制不足以减少疾病传播。因此,除了改善卫生条件和引进新药等其他策略外,疫苗对于成功控制并最终根除血吸虫病至关重要。为此,我们将功能重要的抗原 Sm-p80 作为候选疫苗。在本研究中,Sm-p80 的全长 cDNA 被克隆到 VR1020(FDA 批准的人类使用载体)中。该疫苗制剂的保护功效在小鼠模型中进行了测试。 Sm-p80-VR1020 疫苗配方能够使蠕虫负担减少 47%。对从接种疫苗的动物获得的样本进行血清学分析显示,存在强烈的抗体反应,其中包括 IgG 及其所有亚型、IgM 和 IgA。通过 RT-PCR 分析确定,增殖的脾细胞响应重组 Sm-p80 产生代表 Th1、Th2 和 Th17 类型的多种细胞因子。这些发现进一步强化了 Sm-p80 分子作为肠血吸虫病候选疫苗的重要性。
Although there is an effective drug (praziquantel) available for the treatment of schistosomiasis, yet the disease is still spreading unabated and is rampant in 76 countries. Control via praziquantel treatment has so far been insufficient in reducing the disease transmission. Therefore a vaccine in addition to other strategies, for example, improving sanitation and introduction of new drugs are essential to successfully control and eventually eradicate schistosomiasis. To this effect we have targeted a functionally important antigen, Sm-p80 as a vaccine candidate. In the present study, full length cDNA of Sm-p80 was cloned in VR1020, a FDA approved vector for human use. The protective efficacy of this vaccine formulation was tested in a murine model. Sm-p80-VR1020 vaccine formulation was able to induce 47% reduction in worm burden. Serology on samples obtained from vaccinated animals revealed a strong antibody response which included IgG and all of its subtypes, IgM and IgA. Proliferating splenocytes in response to recombinant Sm-p80 produced a wide spectrum of cytokines representing Th1, Th2 and Th17 types, as ascertained via RT-PCR analysis. These findings further strengthen the importance of Sm-p80 molecule as a vaccine candidate for intestinal schistosomiasis.
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