Ross T M, Xu Y, Green T D, Montefiori D C, Robinson H L
Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, North Carolina 27858, USA.
AIDS Res Hum Retroviruses. 2001 Jun 10;17(9):829-35. doi: 10.1089/088922201750252025.
DNA vaccination can elicit both humoral and cellular immune responses and can confer protection against several pathogens. However, DNA vaccines expressing the envelope (Env) protein of human immunodeficiency virus (HIV) have been relatively ineffective at generating high titer, long-lasting, neutralizing antibodies in a variety of animal models. In this study, we report that fusion of Env and the complement component, C3d, in a DNA vaccine, enhances the titers of antibody to Env. Plasmids were generated that expressed a secreted form of Env (sgp120) from three isolates of HIV and these same forms fused to three tandem copies of the murine homologue of C3d (sgp120-3C3d). Analyses of titers and avidity maturation of the raised antibody indicated that immunizations with each of the sgp120-3C3d-expressing DNAs accelerated both the onset and the avidity maturation of antibody to Env.
DNA疫苗可引发体液免疫和细胞免疫反应,并能提供针对多种病原体的保护。然而,在多种动物模型中,表达人类免疫缺陷病毒(HIV)包膜(Env)蛋白的DNA疫苗在产生高滴度、持久的中和抗体方面相对无效。在本研究中,我们报告称,在DNA疫苗中Env与补体成分C3d融合,可提高针对Env的抗体滴度。构建了表达来自HIV三个分离株的分泌形式Env(sgp120)的质粒,以及这些相同形式与小鼠C3d同源物的三个串联拷贝融合的质粒(sgp120-3C3d)。对产生的抗体的滴度和亲和力成熟度分析表明,用每种表达sgp120-3C3d的DNA进行免疫接种,均可加速针对Env的抗体的产生和亲和力成熟。