Davtyan Hayk, Hovakimyan Armine, Zagorski Karen, Davtyan Arpine, Petrushina Irina, Agdashian David, Murthy Vidya, Cribbs David H, Agadjanyan Michael G, Ghochikyan Anahit
Institute for Molecular Medicine, Huntington Beach, CA 92647, USA.
Curr Gene Ther. 2014;14(3):190-9. doi: 10.2174/1566523214666140522121427.
DNA vaccines promote immune system activation in small animals and exhibit certain advantages when compared to conventional recombinant protein vaccines. However in clinical trials DNA vaccines are less effective in inducing potent immune responses due to the low delivery efficiency and expression of antigens. Currently, various delivery devices such as gene-guns, bioinjectors and electroporation systems are being used in order to increase the potency of DNA vaccines. However, the optimal delivery parameters are required and must be carefully set to obtain the highest levels of gene expression and strong immune responses in humans. The focus of this study was to optimize electroporation settings (voltage, pulse length, pulse intervals, and number of pulses), as well as the route of administration (intradermal vs. intramuscular) and dosage of the DNA epitope vaccine, AV-1959D, delivered by the BTX AgilePulse(TM) system. As a result, we have chosen the optimal settings for electroporation delivery using different routes of immunization with this vaccine, generating (i) robust antibody production to the B cell epitope (a small peptide, derived from β-amyloid), and (ii) strong cellular immune responses to Th epitopes (a small synthetic peptide and eleven peptides from various pathogens) incorporated into DNA vaccine platform.
DNA疫苗可促进小动物的免疫系统激活，与传统重组蛋白疫苗相比具有一定优势。然而，在临床试验中，由于抗原递送效率低和表达水平低，DNA疫苗在诱导强效免疫反应方面效果较差。目前，为了提高DNA疫苗的效力，正在使用各种递送装置，如基因枪、生物注射器和电穿孔系统。然而，需要确定最佳递送参数，并且必须仔细设定以在人体中获得最高水平的基因表达和强烈的免疫反应。本研究的重点是优化电穿孔设置（电压、脉冲长度、脉冲间隔和脉冲次数），以及DNA表位疫苗AV-1959D的给药途径（皮内注射与肌肉注射）和剂量，该疫苗由BTX AgilePulse(TM)系统递送。结果，我们选择了使用该疫苗不同免疫途径进行电穿孔递送的最佳设置，产生了（i）针对B细胞表位（一种源自β-淀粉样蛋白的小肽）的强大抗体产生，以及（ii）对掺入DNA疫苗平台的Th表位（一种小合成肽和来自各种病原体的11种肽）的强烈细胞免疫反应。
