Augmented induction of CD8+ cytotoxic T-cell response and antitumor effect by DCs pulsed with virus-like particles packaging with CpG.
The present study aims at establishing a novel vaccine procedure based on HBc-VLP-pulsed DCs. Immature mice BMDCs could capture HBc-VLP or HBc-VLP packaging CpG efficiently and present the antigen to syngeneic mice spleen T cells in vitro. Immunization with DCs showed that compared to VLP-pulsed DCs, VLP packaging CpG-pulsed DCs elicit stronger T-cell responses in vivo, as measured by both intracellular production of IFN-gamma and in vivo killing assays by Ag-specific T cells. In the B16-pIR-HH tumor therapy model, the growth of established tumors was significantly inhibited by single immunization of DCs pulsed with HBc-VLP packaged with CpG, resulting in significantly longer survival of immunized animals and strikingly, high frequencies (>10% of CD8(+) cells) of protective CTL could be induced and maintained. The mice immunized with DCs treated with HBc-VLP, however, trigger an antitumor effect at the early phase of vaccination, after 20 days of tumor injection, the tumor growth inhibition of VLP-pulsed DCs vaccination was decreased gradually and the fact could be interpreted by the decreasing number of antigen-specific CD8(+) T-cell and IFN-gamma(+)-producing CD8(+) T cell. This study therefore shows that the use of HBc-VLP packaging CpG-pulsed DCs could facilitate the development of effective T-cell-based vaccines.
Song
Shuxia
S
Department of Medical Genetics, Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, PR China. shsun@vip.sina.com
Wang
Yue
Y
Zhang
Yan
Y
Wang
Fang
F
He
Ying
Y
Ren
Ding
D
Guo
Yingjun
Y
Sun
Shuhan
S
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D006509:Hepatitis B / Q000276:immunology / Q000473:pathology / Q000628:therapy; D006512:Hepatitis B Core Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology; D006801:Humans; D007114:Immunization; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D009838:Oligodeoxyribonucleotides; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014771:Virion / Q000276:immunology*
C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D006512:Hepatitis B Core Antigens; D009838:Oligodeoxyribonucleotides; D007371:Interferon-gamma