摘要
DNA疫苗能促进小型动物免疫系统的激活,相比常规的重组蛋白疫苗表现出一定的优势。然而,在临床试验中由于抗原的低投递效率及表达,DNA疫苗诱导免疫应答效应较低。目前,各种药物投递装置例如基因枪、生物注射器、电穿孔系统都已经被用来提高DNA疫苗的效力。但是,获得最佳的投递参数是必需的,且必须仔细地设置来获得对于人类的最高水平基因表达和强免疫反应。本研究使用AV-1959D 疫苗,用BTX AgilePulse系统投递,研究重点是优化电穿孔设置(电压、脉冲持续时间、脉冲间隔和脉冲的数量)以及给药途径(皮内和肌肉)和DNA表位疫苗的剂量。因而,在采用了电穿孔投递的最佳设定条件,使用不同的免疫接种方式来接种这种疫苗,生成了(i)B细胞抗原表位(一个短链多肽,由β-淀粉样蛋白衍生)的高活性抗体并 (ii)产生强的对Th抗原(一个合成的短链多肽和11个从各种病原体中得到的多肽)的细胞免疫应答,且纳入DNA疫苗平台。
关键词: AV-1959D疫苗,电穿孔设备, 免疫应答,皮内投递,肌注投递,BTX AgilePulseTM系统的优化,质粒免疫
Current Gene Therapy
Title:BTX AgilePulseTM System is an Effective Electroporation Device for Intramuscular and Intradermal Delivery of DNA Vaccine
Volume: 14 Issue: 3
Author(s): Hayk Davtyan, Armine Hovakimyan, Karen Zagorski, Arpine Davtyan, Irina Petrushina, David Agdashian, Vidya Murthy, David H. Cribbs, Michael G. Agadjanyan and Anahit Ghochikyan
Affiliation:
关键词: AV-1959D疫苗,电穿孔设备, 免疫应答,皮内投递,肌注投递,BTX AgilePulseTM系统的优化,质粒免疫
摘要: 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 AgilePulseTM 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.
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Davtyan Hayk, Hovakimyan Armine, Zagorski Karen, Davtyan Arpine, Petrushina Irina, Agdashian David, Murthy Vidya, Cribbs H. David, Agadjanyan G. Michael and Ghochikyan Anahit, BTX AgilePulseTM System is an Effective Electroporation Device for Intramuscular and Intradermal Delivery of DNA Vaccine, Current Gene Therapy 2014; 14 (3) . https://dx.doi.org/10.2174/1566523214666140522121427
DOI https://dx.doi.org/10.2174/1566523214666140522121427 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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