摘要
尽管已经存在有效的预防性疫苗,慢性乙肝病毒感染仍旧是一个严重的公共卫生问题。因为微弱的和功能受损的病毒特异性免疫应答在乙肝病毒的持续感染中起关键作用;针对这些应答的刺激似乎对病毒清除特别重要。就此而言,DNA疫苗已经作为一种新颖的、有希望的治疗慢性乙肝的途径。这篇综述介绍了前沿的动物模型(鼠、黑猩猩、鸭、土拨鼠)的临床前研究;这些研究对基因疫苗治疗肝炎病毒蛋白的能力进行了评估,包括诱导小动物持续有效的免疫应答,增强慢性乙肝病毒携带者的病毒清除力和破坏免疫耐受性。为了优化DNA疫苗,我们已经发展和评估了多种策略,包括基因佐剂、抗病毒复合药、加强免疫养生法和质粒投递。采用体内电穿孔法的DNA投递而增加大型、小型动物模型疫苗效力方面的研究引起特别的关注。虽然慢性乙肝的有效治疗需要等待疫苗效力的进一步改善,但是基于临床前研究的满意结果,第一个DNA疫苗的临床试验已经启动。
关键词: DNA疫苗,乙肝病毒,土拨鼠乙肝病毒(WHB),鸭乙肝病毒(DHBV),乙型肝炎,电穿孔法,免疫疗法
Current Gene Therapy
Title:Advances and Challenges in the Development of Therapeutic DNA Vaccines Against Hepatitis B Virus Infection
Volume: 14 Issue: 3
Author(s): Lucyna Cova
Affiliation:
关键词: DNA疫苗,乙肝病毒,土拨鼠乙肝病毒(WHB),鸭乙肝病毒(DHBV),乙型肝炎,电穿孔法,免疫疗法
摘要: Despite the existence of an effective prophylactic vaccine, chronic hepatitis B virus (HBV) infection remains a major public health problem. Because very weak and functionally impaired virus-specific immune responses play a key role in the persistence of HBV infection, the stimulation of these responses appears to be of particular importance for virus clearance. In this regard DNA-based vaccination has emerged as novel, promising therapeutic approach for chronic hepatitis B. This review provides an update of preclinical studies in animal models (mouse, chimpanzee, duck, woodchuck), which evaluated the ability of DNA vaccines targeting hepadnaviral proteins to induce potent and sustained immune responses in naïve animals and to enhance virus clearance and break immune tolerance in chronic virus-carriers. Different strategies have been developed and evaluated in these models to optimize DNA vaccine including genetic adjuvants, combination with antiviral drugs, prime-boost regimens and plasmid delivery. The delivery of DNA by in vivo electroporation appears to be of particular interest for increase of vaccine potency in both small and large animal models. Based on the promising results generated in preclinical studies, first clinical trials of DNA vaccines have been initiated, although effective therapy of chronic hepatitis B awaits further improvements in vaccine efficacy.
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Cite this article as:
Cova Lucyna, Advances and Challenges in the Development of Therapeutic DNA Vaccines Against Hepatitis B Virus Infection, Current Gene Therapy 2014; 14 (3) . https://dx.doi.org/10.2174/1566523214666140509102644
DOI https://dx.doi.org/10.2174/1566523214666140509102644 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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