Coimmunization with RANTES plasmid polarized Th1 immune response against hepatitis B virus envelope via recruitment of dendritic cells

Abstract

Induction of T help cell type 1 (Th1) response seems to be a prerequisite of HBV clearance. DNA vaccines have shown its potential to elicit Th1-biased immune response. However, its immunogenicity needs to be improved. Regulated upon activation normal T cell expressed and secreted (RANTES) is an inflammatory chemokine that promotes the accumulation and activation of CD4+, CD8+ T cells, and dendritic cells (DCs), which would favor antiviral immunity. In this study, the efficacy of a DNA vaccine encoding hepatitis B virus (HBV) preS2 plus S protein was enhanced through co-injection of a plasmid encoding RANTES in a BALB/c model. Co-injection of RANTES gene resulted in a moderate increase in the HBV specific humoral and cellular immune responses and a significant increase following an HBsAg booster vaccination compared to DNA encoding HBsAg alone. This enhancement was due to an enrichment of DCs in the draining lymph node and an up-regulation of DCs maturation by RANTES. More importantly, RANTES polarized the specific immunity towards a dominant Th1 profile and even converted an established Th2 response to a Th1 phenotype. Our study suggested the feasibility of using a plasmid-encoded RANTES as a modulatory Th1 adjuvant in genetic vaccination.