Coimmunization with RANTES plasmid polarized Th1 immune response against hepatitis B virus envelope via recruitment of dendritic cells.
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.
Ma
Ke
K
Institute for ImmunoBiology and Department of Immunology, Shanghai Medical College of Fudan University, 138, Yi Xue Yuan Road, Shanghai 200032, PR China.
Xu
Wei
W
Shao
Xianan
X
Yanyue
Hu
Linkun
L
Xu
Huanbin
H
Yuan
Zhigang
Z
Zheng
Xiujuan
X
Xiong
Sidong
S
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000235:genetics / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D007117:Immunization, Secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
D000914:Antibodies, Viral; D018946:Chemokine CCL5; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D011498:Protein Precursors; D019444:Vaccines, DNA; C050807:presurface protein 2, hepatitis B surface antigen