Pachuk C J, McCallus D E, Weiner D B, Satishchandran C
Wyeth-Lederie Vaccines, One Great Valley Parkway, Malvern, PA 19355, USA.
Curr Opin Mol Ther. 2000 Apr;2(2):188-98.
DNA vaccines are typically comprised of plasmid DNA molecules that encode an antigen(s) derived from a pathogen or tumor cell. Following introduction into a vaccine, cells take up the DNA, where expression and immune presentation of the encoded antigen(s) takes place. DNA can be introduced by viral or bacterial vectors or through uptake of 'naked' or complexed DNA. Vaccination with DNA is a recent technology possessing distinct advantages over traditional vaccines (killed or attenuated pathogens) and the more recently developed subunit vaccines. Unlike most subunit vaccines, DNA vaccines induce both the humoral and cellular arms of the immune response. The stimulation of both arms of the immune system is important not only for the prevention of many diseases including AIDS, but also allows the use of a vaccine for therapeutic purposes. While the traditional attenuated pathogen vaccines are also able to elicit both cellular and humoral immune responses, there is a risk of reversion from the attenuated state to the virulent state. This risk does not exist with DNA vaccines. DNA vaccines can be manufactured and formulated by generic processes. DNA vaccine technology, however, is still in its infancy and much research needs to be done to improve the efficiency with which these vaccines work in humans. While continued efforts toward improving both DNA expression and DNA delivery are equally important for increasing the utility of DNA vaccines, this review will focus both on non-viral delivery of plasmid DNA and delivery methods for the encoded antigen.
DNA疫苗通常由质粒DNA分子组成,这些分子编码源自病原体或肿瘤细胞的一种或多种抗原。引入疫苗后,细胞摄取DNA,在其中发生编码抗原的表达和免疫呈递。DNA可通过病毒或细菌载体引入,或通过摄取“裸”DNA或复合DNA引入。DNA疫苗接种是一项新技术,与传统疫苗(灭活或减毒病原体)以及最近开发的亚单位疫苗相比具有明显优势。与大多数亚单位疫苗不同,DNA疫苗可诱导免疫反应的体液免疫和细胞免疫分支。刺激免疫系统的两个分支不仅对预防包括艾滋病在内的许多疾病很重要,而且还允许将疫苗用于治疗目的。虽然传统的减毒病原体疫苗也能够引发细胞免疫和体液免疫反应,但存在从减毒状态回复到致病状态的风险。DNA疫苗不存在这种风险。DNA疫苗可以通过通用工艺制造和配制。然而,DNA疫苗技术仍处于起步阶段,需要进行大量研究以提高这些疫苗在人体中的工作效率。虽然持续努力改进DNA表达和DNA递送对于提高DNA疫苗的效用同样重要,但本综述将重点关注质粒DNA的非病毒递送以及编码抗原的递送方法。