Cohen A D, Boyer J D, Weiner D B
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
FASEB J. 1998 Dec;12(15):1611-26.
Genetic immunization, also known as DNA or polynucleotide immunization, is a novel strategy for vaccine development in which plasmid DNA encoding either individual or a collection of antigens is directly administered to a host. Such immunization leads to host expression of the delivered foreign gene, resulting in the induction of a specific immune response against the in vivo produced antigen. DNA immunization has been shown to induce protective immune responses in several infectious disease and cancer experimental model systems. Furthermore, DNA vaccines have recently entered the clinic for analysis as both prophylactic and therapeutic agents. Although the mechanisms of immunity to DNA have not yet been fully elucidated, it has become apparent that the immune response achieved by DNA vaccination is quite malleable, and can be manipulated by altering the conditions under which the vaccine is administered. Either through changing the method or location of immunization, altering the number of immunostimulatory sequences in the plasmid, altering the immunization regimen, or coadministering genes for cytokines or costimulatory molecules, one can modulate both the magnitude and orientation of the subsequent immune response. Through maximization of this feature of DNA immunization, we will likely be able to design vaccines and immunotherapeutic agents that are tailored to the correlates of protection for a particular disease, resulting in a new generation of more focused and effective immune stimulating agents.
基因免疫，也称为DNA或多核苷酸免疫，是一种新型疫苗研发策略，即将编码单个或一组抗原的质粒DNA直接导入宿主。这种免疫可使导入的外源基因在宿主体内表达，从而诱导针对体内产生的抗原的特异性免疫反应。在多种传染病和癌症实验模型系统中，DNA免疫已被证明可诱导保护性免疫反应。此外，DNA疫苗最近已进入临床，作为预防和治疗药物进行分析。尽管对DNA免疫的机制尚未完全阐明，但很明显，DNA疫苗接种所产生的免疫反应具有很大的可塑性，可通过改变疫苗接种的条件来加以调控。无论是通过改变免疫方法或部位、改变质粒中免疫刺激序列的数量、改变免疫方案，还是共同给予细胞因子或共刺激分子的基因，都可以调节后续免疫反应的强度和方向。通过充分利用DNA免疫的这一特性，我们很可能能够设计出针对特定疾病保护相关因素的疫苗和免疫治疗药物，从而产生新一代更具针对性和有效性的免疫刺激剂。
