Dupré L, Poulain-Godefroy O, Ban E, Ivanoff N, Mekranfar M, Schacht A M, Capron A, Riveau G
Inserm U 167, Institut Pasteur de Lille, France.
Parasite Immunol. 1997 Nov;19(11):505-13. doi: 10.1046/j.1365-3024.1997.d01-163.x.
Direct administration of plasmid DNA encoding an antigen represents an attractive approach to vaccination against infectious diseases, particularly in developing countries where easy-to-handle and cost-effective vaccines are needed. We have investigated the potential of DNA immunization to induce a specific antibody response against Schistosoma mansoni, using plasmid-DNA encoding the protective antigen, S. mansoni 28 kDa glutathione S-transferase (Sm28GST). Since S. mansoni parasite penetrates into its host through the skin, this tissue was chosen for plasmid DNA delivery. Following plasmid DNA administration into the skin of rats, the parasite antigen was detected in skin cells by immunohistochemistry. Three administrations of 200 micrograms plasmid at 14 day intervals led to the induction of a long-lasting specific IgG antibody response in the sera of immunized rats, with a predominance of IgG2a and IgG2b subclasses. Sera of immunized animals were able to mediate antibody-dependent cellular cytotoxicity in vitro, leading to the specific killing of parasite larvae. A parasite challenge performed on plasmid DNA-immunized animals induced a strong and rapid boosting effect on the specific IgG antibody response. These results demonstrate the potential of genetic immunization via the skin with plasmid DNA encoding Sm28GST for inducing immune responses with protective patterns against an S. mansoni infection.
直接给予编码抗原的质粒DNA是一种针对传染病进行疫苗接种的有吸引力的方法,特别是在需要易于处理且具有成本效益的疫苗的发展中国家。我们研究了DNA免疫诱导针对曼氏血吸虫特异性抗体反应的潜力,使用编码保护性抗原曼氏血吸虫28 kDa谷胱甘肽S-转移酶(Sm28GST)的质粒DNA。由于曼氏血吸虫通过皮肤侵入宿主,因此选择该组织进行质粒DNA递送。将质粒DNA注入大鼠皮肤后,通过免疫组织化学在皮肤细胞中检测到寄生虫抗原。每隔14天给予200微克质粒,共给药三次,可在免疫大鼠血清中诱导持久的特异性IgG抗体反应,其中以IgG2a和IgG2b亚类为主。免疫动物的血清能够在体外介导抗体依赖性细胞毒性,导致寄生虫幼虫的特异性杀伤。对质粒DNA免疫动物进行的寄生虫攻击对特异性IgG抗体反应诱导了强烈而快速的增强作用。这些结果证明了通过皮肤用编码Sm28GST的质粒DNA进行基因免疫诱导针对曼氏血吸虫感染的具有保护模式的免疫反应的潜力。