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DNA疫苗:基本机制与免疫反应(综述)

DNA vaccines: basic mechanism and immune responses (Review).

作者信息

Robinson H L

机构信息

Yerkes Primate Research Center, Atlanta, GA 30329, USA.

出版信息

Int J Mol Med. 1999 Nov;4(5):549-55. doi: 10.3892/ijmm.4.5.549.

Abstract

DNA vaccines raise immune responses by expressing proteins in vaccinated hosts. Responses are raised by nanogram levels of protein expression. Popular methods of DNA delivery include intramuscular (i. m.) injections of DNA in saline and gene gun delivery of DNA-coated gold beads to the epidermis. Professional antigen-presenting cells derived from the bone marrow present DNA-expressed antigens to T-cells. Following gene gun immunizations directly transfected dendritic cells present antigens, whereas following i.m. immunizations both directly transfected dendritic cells and macrophages can present antigen. For both methods of DNA delivery, non-lymphoid cells can serve as factories of antigen for professional antigen presenting cells. Gene gun immunizations depend on antigen expression at the skin target whereas i.m. immunizations are largely independent of DNA expression in the muscle target. For both methods, antigen expression capable of initiating an immune response persists for about one month. intramuscular deliveries of DNA tend to raise type 1 T-cell help for intracellular and plasma membrane antigens but type 2 T-cell help for secreted antigens. Gene gun immunizations tend to raise type 2 T-cell help for both cell-associated and secreted antigens. In mice, DNA-raised immune responses can be equivalent to those raised by viral infections for both the height and longevity of antibody and cytotoxic T-cell responses.

摘要

DNA疫苗通过在接种宿主中表达蛋白质来引发免疫反应。纳克水平的蛋白质表达即可引发反应。常见的DNA递送方法包括将DNA注射到盐水中进行肌肉注射,以及使用基因枪将包被有DNA的金珠递送至表皮。源自骨髓的专业抗原呈递细胞将DNA表达的抗原呈递给T细胞。基因枪免疫后,直接转染的树突状细胞呈递抗原,而肌肉注射免疫后,直接转染的树突状细胞和巨噬细胞均可呈递抗原。对于这两种DNA递送方法,非淋巴细胞都可作为专业抗原呈递细胞的抗原工厂。基因枪免疫依赖于皮肤靶点处的抗原表达,而肌肉注射免疫在很大程度上不依赖于肌肉靶点处的DNA表达。对于这两种方法,能够引发免疫反应的抗原表达可持续约一个月。肌肉注射DNA往往会引发针对细胞内和细胞膜抗原的1型T细胞辅助,但针对分泌性抗原则引发2型T细胞辅助。基因枪免疫往往会针对细胞相关抗原和分泌性抗原引发2型T细胞辅助。在小鼠中,就抗体和细胞毒性T细胞反应的强度和持续时间而言,DNA引发的免疫反应可与病毒感染引发的反应相当。

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