首页> 外文期刊>Infection and immunity >A Bicistronic DNA Vaccine Containing Apical Membrane Antigen 1 and Merozoite Surface Protein 4/5 Can Prime Humoral and Cellular Immune Responses and Partially Protect Mice against Virulent Plasmodium chabaudi adami DS Malaria
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A Bicistronic DNA Vaccine Containing Apical Membrane Antigen 1 and Merozoite Surface Protein 4/5 Can Prime Humoral and Cellular Immune Responses and Partially Protect Mice against Virulent Plasmodium chabaudi adami DS Malaria

机译:包含顶膜抗原1和裂殖子表面蛋白4/5的双顺反子DNA疫苗可以引发体液和细胞的免疫反应,并部分保护小鼠免于感染Chabaudi adami DS恶性疟原虫。

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The ultimate malaria vaccine will require the delivery of multiple antigens from different stages of the complex malaria life cycle. In order to efficiently deliver multiple antigens with use of DNA vaccine technology, new antigen delivery systems must be assessed. This study utilized a bicistronic vector construct, containing an internal ribosome entry site, expressing a combination of malarial candidate antigens: merozoite surface protein 4/5 (MSP4/5) (fused to a monocyte chemotactic protein 3 chemoattractant sequence) and apical membrane antigen 1 (AMA-1) (fused to a tissue plasminogen activator secretion signal). Transfection of COS 7 cells with bicistronic plasmids resulted in production and secretion of both AMA-1 and MSP4/5 in vitro. Vaccination of BALB/c mice via intraepidermal gene gun and intramuscular routes against AMA-1 and MSP4/5 resulted in antibody production and significant in vitro proliferation of splenocytes stimulated by both AMA-1 and MSP4/5. Survival of BALB/c mice vaccinated with bicistronic constructs after lethal Plasmodium chabaudi adami DS erythrocytic-stage challenge was variable, although significant increases in survival and reductions in peak parasitemia were observed in several challenge trials when the vaccine was delivered by the intramuscular route. This study using a murine model demonstrates that the delivery of malarial antigens via bicistronic vectors is feasible. Further experimentation with bicistronic delivery systems is required for the optimization and refinement of DNA vaccines to effectively prime protective immune responses against malaria.
机译:最终的疟疾疫苗将需要从复杂疟疾生命周期的不同阶段传递多种抗原。为了使用DNA疫苗技术有效地输送多种抗原,必须评估新的抗原输送系统。这项研究利用了双顺反子载体构建体,该构建体包含一个内部核糖体进入位点,可表达疟疾候选抗原的组合:裂殖子表面蛋白4/5(MSP4 / 5)(与单核细胞趋化蛋白3趋化因子序列融合)和顶膜抗原1 (AMA-1)(与组织纤溶酶原激活物的分泌信号融合)。用双顺反子质粒转染COS 7细胞导致体外产生和分泌AMA-1和MSP4 / 5。通过表皮内基因枪和肌内途径针对AMA-1和MSP4 / 5对BALB / c小鼠进行疫苗接种可导致抗体产生以及受AMA-1和MSP4 / 5刺激的脾细胞显着体外增殖。致死性 chabaudi adami DS促红细胞生成素阶段性致死疫苗接种双顺反子构建体的BALB / c小鼠的存活率是可变的,尽管在一些挑战性试验中观察到当疫苗接种时,存活率显着增加且峰值寄生虫率降低。通过肌内途径传递。使用鼠模型的这项研究表明,通过双顺反子载体递送疟疾抗原是可行的。需要对双顺反子传递系统进行进一步的实验,以优化和完善DNA疫苗,从而有效引发针对疟疾的保护性免疫应答。

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