A truncated C-terminal fragment of Mycobacterium tuberculosis HSP70 gene enhanced potency of HBV DNA vaccine.
DNA vaccine represents an attractive approach to therapy of chronic hepatitis B virus (HBV) infection because of its ability to generate antigen-specific immunity; nevertheless, there is still a need to increase the potency of DNA vaccine. Mycobacterium tuberculosis heat shock protein70 (HSP70) has both chaperon and cytokine functions, and has been shown to act as an adjuvant when co-administered with peptide antigens or given as fusion proteins. Here we evaluated the effects of two truncated HSP70 molecules, N-terminal domain (HSP70(1-360), amino acids 1-360) and C-terminal domain (HSP70(359-610), amino acids 359-610) of mycobacterial HSP70, on the potency of antigen-specific immunity generated by a HBV DNA vaccination. We found that only the HSP70(359-610)-fused HBV DNA vaccination resulted in a significant increase in hepatitis B surface antigen (HBsAg)-specific humoral response, while the HSP70(1-360)- or the complete HSP70 molecule-fused vaccine did not. Moreover, HSP70(359-610)-fused DNA vaccine did not induce anti-HSP70 antibody. Interestingly, HSP70(359-610) not only enhanced HBsAg-specific cytotoxic lymphocytes (CTL) responses but also overcame the epitope suppression caused by L(d)-restricted epitope. Meanwhile, HSP70(369-610) mediated T helper (Th) cell balance towards Th1 pathway. In a HBV transgenic mouse model, the HSP70(359-610) fusion vaccine facilitated clearance of circulating HBsAg and down-regulation of HBV replication. These results suggested that the truncated mycobacterial HSP70 molecule, HSP70(359-610), might be a superior candidate to deliver the adjuvant function in HBV DNA vaccination instead of the complete HSP70 molecule.
Li
Xiangming
X
School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, PR China.
Yang
Xiaofeng
X
Li
Liangwei
L
Liu
Haibo
H
Liu
Jing
J
D000276:Adjuvants, Immunologic; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000276:immunology*; D006509:Hepatitis B / Q000628:therapy; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000235:genetics / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014779:Virus Replication
D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA