Enhanced avidity maturation of antibody to human immunodeficiency virus envelope: DNA vaccination with gp120-C3d fusion proteins

DNA vaccination can elicit both humoral and cellular immune responses and c an confer protection against several pathogens. However, DNA vaccines expre ssing the envelope (Env) protein of human immunodeficiency virus (HIV) have been relatively ineffective at generating high titer, long-lasting, neutra lizing antibodies in a variety of animal models. In this study, we report t hat fusion of Env and the complement component, C3d, in a DNA vaccine, enha nces 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 f orms fused to three tandem copies of the murine homologue of C3d (sgp120-3C 3d). Analyses of titers and avidity maturation of the raised antibody indic ated that immunizations with each of the sgp120-3C3d-expressing DNAs accele rated both the onset and the avidity maturation of antibody to Env.