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基于 Sm-p80 的 DNA 疫苗在经过人类使用批准的 VR1020 载体中制成,可预防小鼠感染曼氏血吸虫的挑战感染。

Sm-p80-based DNA vaccine made in a human use approved vector VR1020 protects against challenge infection with Schistosoma mansoni in mouse.

机构信息

Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.

出版信息

Parasite Immunol. 2010 Apr;32(4):252-8. doi: 10.1111/j.1365-3024.2009.01181.x.

Abstract

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 this 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.

摘要

尽管有有效的药物(吡喹酮)可用于治疗血吸虫病,但该疾病仍在继续蔓延,在 76 个国家肆虐。迄今为止,通过吡喹酮治疗来控制该疾病的传播还远远不够。因此,除了其他策略(例如改善卫生条件和引入新药)之外,疫苗对于成功控制和最终消除血吸虫病也是必不可少的。为此,我们选择了一个功能重要的抗原 Sm-p80 作为疫苗候选物。在这项研究中,Sm-p80 的全长 cDNA 被克隆到了 VR1020 中,这是一种已获得 FDA 批准可用于人体的载体。在小鼠模型中测试了这种疫苗制剂的保护效力。Sm-p80-VR1020 疫苗制剂能够将虫荷减少 47%。对来自接种动物的样本进行的血清学检测显示出强烈的抗体反应,包括 IgG 及其所有亚型、IgM 和 IgA。用重组 Sm-p80 刺激的脾细胞产生了广泛的细胞因子谱,通过 RT-PCR 分析确定了这些细胞因子属于 Th1、Th2 和 Th17 型。这些发现进一步证实了 Sm-p80 分子作为肠道血吸虫病疫苗候选物的重要性。

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