DNA Vaccination by Electroporation and Boosting with Recombinant Proteins Enhances the Efficacy of DNA Vaccines for Schistosomiasis Japonica
DNA Vaccination by Electroporation and Boosting with Recombinant Proteins Enhances the Efficacy of DNA Vaccines for Schistosomiasis Japonica
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DOI：
10.1128/cvi.00231-09
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发表时间：
2009-12-01
影响因子：
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通讯作者：
Guan, Xiaohong
中科院分区：
文献类型：
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作者：
Dai, Yang;Zhu, Yinchang;Guan, Xiaohong
日本血吸虫病是一种地方性人兽共患传染病，在我国具有重要的公共卫生意义。结合化疗和灭螺的控制方案未能阻止湖泊和沼泽地区的感染传播。需要接种疫苗作为正在进行的控制方案的补充方法。在本研究中，我们希望确定是否可以通过体内电穿孔和/或鸡尾酒蛋白疫苗加强编码23 kDa四跨膜蛋白（SjC 23），磷酸丙糖异构酶（SjCTPI）和NP 30的H链中的互补决定区3（CDR 3）的六倍重复基因的DNA疫苗的效力。结果表明，混合DNA疫苗免疫小鼠，减虫率为32.88%（P < 0.01），减卵率为36.20%（P < 0.01）。当动物用鸡尾酒蛋白疫苗加强免疫时，疫苗效力增强;成虫和肝卵负荷分别降低45.35%和48.54%。电穿孔免疫小鼠的结果与电穿孔免疫小鼠的结果基本一致，成虫和虫卵负荷分别降低了45.00%和50.88%。向该方案中添加蛋白疫苗加强，进一步将成虫负荷的有效性提高至约60%，并将肝卵减少率提高至大于60%。白细胞介素-2、γ干扰素水平和免疫球蛋白G2 a（IgG 2a）/IgG 1比值清楚地表明，鸡尾酒DNA疫苗诱导了CD 4（+）Th 1型应答。通过电穿孔或重组蛋白的加强显著增加了相关的免疫应答，超过了仅用DNA疫苗接种的小鼠中观察到的免疫应答。因此，通过体内电穿孔和/或鸡尾酒蛋白疫苗的加强，双链体DNA疫苗功效显著增强。
Schistosomiasis japonica is an endemic, zoonotic disease of major public health importance in China. Control programs combining chemotherapy and snail killing have not been able to block transmission of infection in lakes and marsh regions. Vaccination is needed as a complementary approach to the ongoing control programs. In the present study, we wanted to determine if the efficacies of DNA vaccines encoding the 23-kDa tetraspanin membrane protein (SjC23), triose phosphate isomerase (SjCTPI), and sixfold-repeated genes of the complementarity determining region 3 (CDR3) in the H chain of NP30 could be enhanced by boosting via electroporation in vivo and/or with cocktail protein vaccines. Mice vaccinated with cocktail DNA vaccines showed a significant worm reduction of 32.88% (P < 0.01) and egg reduction of 36.20% ( P < 0.01). Vaccine efficacy was enhanced when animals were boosted with cocktail protein vaccines; adult worm and liver egg burdens were reduced 45.35% and 48.54%, respectively. Nearly identical results were obtained in mice boosted by electroporation in vivo, with adult worm and egg burdens reduced by 45.00% and 50.88%, respectively. The addition of a protein vaccine boost to this regimen further elevated efficacy to approximately 60% for adult worm burden and greater than 60% for liver egg reduction. The levels of interleukin-2, gamma interferon, and the ratios of immunoglobulin G2a (IgG2a)/IgG1 clearly showed that cocktail DNA vaccines induced CD4(+) Th1-type responses. Boosting via either electroporation or with recombinant proteins significantly increased associated immune responses over those seen in mice vaccinated solely with DNA vaccines. Thus, schistosome DNA vaccine efficacy was significantly enhanced via boosting by electroporation in vivo and/or cocktail protein vaccines.