Induction of robust immunity by the emulsification of recombinant lipidated dengue-1 envelope protein domain III

Abstract

Many attempts have focused on the use of either immunomodulators or antigen delivery systems to obtain an efficacious vaccine. Here, we report a novel approach that combined an immunomodulator and delivery system to enhance antigen association and induce robust immunity. We expressed a recombinant lipidated dengue-1 envelope protein domain III (LD1ED III) and its non-lipidated form, D1ED III, in an Escherichia coli system. The LD1ED III contains a bacterial lipid moiety, which is a potent immunomodulator. We demonstrated that LD1ED III possesses an inherent immunostimulation ability that can activate RAW 264.7 macrophage cells by up-regulating their expression of CD40, CD80, CD83, CD86 and MHC II, whereas D1ED III could not induce the up-regulation of these molecules. Moreover, combining LD1ED III with a multiphase emulsion system (called PELC) increased the antigen association more than either combining D1ED III with PELC or the antigen alone. Enhanced antigen association has been shown to correlate with stronger T cell responses, greater antibody avidity and improved neutralizing capacity. Our results demonstrate that combining recombinant lipoproteins with PELC improved both the intensity and the quality of the immune response. This approach is a promising strategy for the development of subunit vaccines that induce robust immunity.