DNA 免疫技术在单克隆抗体开发中的研究进展

doi:10.13560/j.cnki.biotech.bull.1985.2018-0643

摘要/Abstract

摘要： DNA免疫是将编码特异性抗原的重组表达载体转入动物体内,特异性基因序列在动物体内得以表达并诱导产生其特异性抗体的一系列免疫应答过程。目前,DNA免疫已成为多种保护性以及诊断性单克隆抗体研究和开发的主要技术手段,尤其对于在体外难以表达和纯化的抗原,DNA免疫比传统的蛋白免疫占绝对优势。DNA免疫在宿主细胞内表达抗原及递呈方式类似于病毒感染,既能产生体液免疫,又能产生细胞免疫,由此克服了传统蛋白质免疫方法的缺陷,为制备高质量单克隆抗体提供了良好的技术平台。然而这项技术在实践应用中遇到了不少挑战,尤其是以传统的肌肉注射法免疫单一的质粒DNA,使递送效率和抗体表达水平都很低,导致DNA免疫的低免疫原性。综述了DNA免疫技术在单克隆抗体开发中的应用,对DNA免疫相关概念、诱导机制、载体的构建、递送方式、不同免疫佐剂的影响、优点和发展前景等方面进行论述,旨在为DNA免疫技术在制备高质量单克隆抗体中的应用以及提高其免疫效率提供有效的理论知识。

关键词: 单克隆抗体, DNA 免疫, 蛋白质免疫

Abstract: DNA immunization refers to a series of immune response processes in which the recombinant expression vector encoding a specific antigen is transferred into animal bodies,and the specific gene sequence is expressed in the animal cells and then induces to produce its specific antibody. At present,DNA immunization has become the main technical means for the research and development of various protective and diagnostic monoclonal antibodies,especially for those antigen that are difficult to express and purify in vitro. DNA immunization is superior to traditional protein immunization. DNA immunization expresses antigen in host cells and its presented manner is similar to viral infection,which can produce both humoral and cellular immunity,thereby overcoming the shortcomings of traditional protein immunization and providing an ideal technology platform for preparing high quality monoclonal antibodies. However,many challenges have been encountered in practical applications of this technique;especially the traditional intramuscular injection method is used to immunize a single plasmid DNA,which results in low delivery efficiency and antibody expression level,then leading to the low immunogenicity of DNA immunization. This article reviews the application of DNA immunoassay in the development of monoclonal antibodies,and to further discusses the DNA immunization technology in terms of its concepts,induction mechanism,vector construction,delivery methods,effects of different immunological adjuvants and its advantages and development prospects. Our aim is to provide an effective theoretical knowledge in the application of DNA immunization technology in preparing high quality monoclonal antibodies and improving its immune efficiency.

Key words: monoclonal antibody, DNA immunization, protein immunization

叶尔那扎尔·努尔吐热, 邱丽芬, 张富春, 张茂祥. DNA 免疫技术在单克隆抗体开发中的研究进展[J]. 生物技术通报, 2019, 35(2): 204-211.

NUERTURE Yeernazhaer, QIU Li-fen, ZHANG Fu-chun, ZHANG Mao-xiang. Research Progress on DNA Immunization Technology in the Development of Monoclonal Antibodies[J]. Biotechnology Bulletin, 2019, 35(2): 204-211.

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