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病毒DNA疫苗的当前进展:它们能解决尚未解决的问题吗?

Current developments in viral DNA vaccines: shall they solve the unsolved?

作者信息

Rajcáni J, Mosko T, Rezuchová I

机构信息

Institute of Virology, Slovak Academy of Sciences, Dúbravská cesta 9, 845 05 Bratislava, Slovak Republic.

出版信息

Rev Med Virol. 2005 Sep-Oct;15(5):303-25. doi: 10.1002/rmv.467.

DOI:10.1002/rmv.467
PMID:15906276
Abstract

This review describes the mechanisms of immune response following DNA vaccination. The efficacy of DNA vaccines in animal models is highlighted, especially in viral diseases against which no widely accepted vaccination is currently available. Emphasis is given to possible therapeutic vaccination in chronic infections due to persisting virus genomes, such as recurrent herpes (HSV-1 and HSV-2), pre-AIDS (HIV-1) and/or chronic hepatitis B (HBV). In these, the problem of introducing foreign viral DNA may not be of crucial importance, since the immunised subject is already a viral DNA (or provirus) carrier. The DNA-based immunisation strategies may overcome several problems of classical viral vaccines. Novel DNA vaccines could induce immunity against multiple viral epitopes including the conservative type common ones, which do not undergo antigenic drifts. Within the immunised host, they mimic the effect of live attenuated viral vaccines when continuously expressing the polypeptide in question. For this reason they directly stimulate the antigen-presenting cells, especially dendritic cells. The antigen encoded by plasmid elicits T helper cell activity (Th1 and Th2 type responses), primes the cytotoxic T cell memory and may induce a satisfactory humoral response. The efficacy of DNA vaccines can be improved by adding plasmids encoding immunomodulatory cytokines and/or their co-receptors.

摘要

本综述描述了DNA疫苗接种后的免疫反应机制。强调了DNA疫苗在动物模型中的有效性,尤其是在目前尚无广泛接受的疫苗的病毒性疾病中。重点讨论了由于病毒基因组持续存在而导致的慢性感染中的可能治疗性疫苗接种,如复发性疱疹(HSV-1和HSV-2)、艾滋病前期(HIV-1)和/或慢性乙型肝炎(HBV)。在这些疾病中,引入外源病毒DNA的问题可能并不至关重要,因为免疫对象已经是病毒DNA(或前病毒)携带者。基于DNA的免疫策略可能克服传统病毒疫苗的几个问题。新型DNA疫苗可以诱导针对多种病毒表位的免疫,包括保守的常见类型,这些表位不会发生抗原漂移。在免疫宿主体内,当它们持续表达相关多肽时,它们模拟减毒活病毒疫苗的效果。因此,它们直接刺激抗原呈递细胞,尤其是树突状细胞。质粒编码的抗原引发T辅助细胞活性(Th1和Th2型反应),启动细胞毒性T细胞记忆,并可能诱导令人满意的体液反应。通过添加编码免疫调节细胞因子和/或其共受体的质粒,可以提高DNA疫苗的效力。

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