Electroporation delivery of DNA vaccines: prospects for success.

Electroporation delivery of DNA vaccines: prospects for success.
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DNA疫苗的电穿孔输送:成功的前景。

DOI:
10.1016/j.coi.2011.03.008
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发表时间:
2011-06
影响因子:
7
通讯作者:
Weiner DB
Weiner DB
中科院分区:
医学2区
文献类型:
--
作者:
Sardesai NY;Weiner DB

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在过去几年中,DNA疫苗研究和开发方面取得了一些值得注意的技术进步,使这一领域重新成为一种可行的疫苗形式。值得注意的是,这些包括- DNA结构的优化;开发新的DNA制造工艺和配方;新型编码分子佐剂增强免疫应答以及包括电穿孔(EP)在内的新的体内给药策略的改进。其中,EP介导的递送引起了相当大的热情,似乎对疫苗的免疫原性和有效性产生了很大的影响,因为抗原递送比单独的裸DNA递送增加了1000倍。与单独直接注射DNA相比,这种增加的递送导致了体内免疫反应强度和反应率的提高。事实上,在许多情况下,通过EP给药DNA后观察到的免疫反应和对病原体的保护与其他经过充分研究的疫苗平台(包括病毒载体和活/减毒/灭活病毒疫苗)相当或优于。值得注意的是,早期在许多不同传染病和癌症的临床前动物模型中显示的EP递送前景,现在正在转化为人类临床试验中同样增强的免疫反应,这使得这种疫苗方法影响多种疾病目标的前景变得切实可行。
A number of noteworthy technology advances in DNA vaccines research and development over the past few years have led to the resurgence of this field as a viable vaccine modality. Notably, these include - optimization of DNA constructs; development of new DNA manufacturing processes and formulations; augmentation of immune responses with novel encoded molecular adjuvants; and the improvement in new in vivo delivery strategies including electroporation (EP). Of these, EP mediated delivery has generated considerable enthusiasm and appears to have had a great impact in vaccine immunegenicity and efficacy by increasing antigen delivery upto a 1000 fold over naked DNA delivery alone. This increased delivery has resulted in an improved in vivo immune response magnitude as well as response rates relative to DNA delivery by direct injection alone. Indeed the immune responses and protection from pathogen challenge observed following DNA administration via EP in many cases are comparable or superior to other well studied vaccine platforms including viral vectors and live/attenuated/inactivated virus vaccines. Significantly, the early promise of EP delivery shown in numerous pre-clinical animal models of many different infectious diseases and cancer are now translating into equally enhanced immune responses in human clinical trials making the prospects for this vaccine approach to impact diverse disease targets tangible.
通过合成共识DNA抗原的体内电穿孔对致病性人类和鸟类流感病毒的杂型保护。
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