Targeting hepatitis B virus antigens to dendritic cells by heat shock protein to improve DNA vaccine potency.
OBJECTIVE
To investigate a novel DNA vaccination based upon expression of the HBV e antigen fused to a heat shock protein (HSP) as a strategy to enhance DNA vaccine potency.


METHODS
A pCMV-HBeAg-HSP DNA vaccine and a control DNA vaccine were generated. Mice were immunized with these different construct. Immune responses were measured 2 wk after a second immunization by a T cell response assay, CTL cytotoxicity assay, and an antibody assay in C57BL/6 and BALB/c mice. CT26-HBeAg tumor cell challenge test in vivo was performed in BALB/c mice to monitor anti-tumor immune responses.


RESULTS
In the mice immunized with pCMV-HBe-HSP DNA, superior CTL activity to target HBV-positive target cells was observed in comparison with mice immunized with pCMV-HBeAg (44% +/- 5% vs 30% +/- 6% in E:T > 50:1, P < 0.05). ELISPOT assays showed a stronger T-cell response from mice immunized with pCMV-HBe-HSP than that from pCMV-HBeAg immunized animals when stimulated either with MHC class I or class II epitopes derived from HBeAg (74% +/- 9% vs 31% +/- 6%, P < 0.01). ELISA assays revealed an enhanced HBeAg antibody response from mice immunized with pCMV-HBe-HSP than from those immunized with pCMV-HBeAg. The lowest tumor incidence and the slowest tumor growth were observed in mice immunized with pCMV-HBe-HSP when challenged with CT26-HBeAg.


CONCLUSIONS
The results of this study demonstrate a broad enhancement of antigen-specific CD4+ helper, CD8+ cytotoxic T-cell, and B-cell responses by a novel DNA vaccination strategy. They also proved a stronger antigen-specific immune memory, which may be superior to currently described HBV DNA vaccination strategies for the treatment of chronic HBV infection.
Gu
Qin-Long
QL
Department of Surgery, Shanghai Institute of Digestive Surgery, Affiliated Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 227 Chongqing Nan Road, Shanghai 200025, China. qlgu@shsmu.edu.cn
Huang
Xue
X
Ren
Wen-Hong
WH
Shen
Lei
L
Liu
Bing-Ya
BY
Chen
Si-Yi
SY
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics / Q000627:therapeutic use*; D006509:Hepatitis B / Q000150:complications / Q000276:immunology / Q000517:prevention & control*; D006513:Hepatitis B e Antigens / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019444:Vaccines, DNA / Q000235:genetics / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
D006360:Heat-Shock Proteins; D006513:Hepatitis B e Antigens; D019444:Vaccines, DNA