Cytotoxic-T-lymphocyte human papillomavirus type 16 E5 peptide with CpG-oligodeoxynucleotide can eliminate tumor growth in C57BL/6 mice.
Previously, we identified human papillomavirus type 16 (HPV-16) E5 as a tumor rejection antigen that can induce cytotoxic T lymphocytes (CTLs) to protect against tumor growth (D. W. Liu et al., J. Virol. 74:9083-9089, 2000). In the present study, we further mapped the CTL epitope of E5 protein by analyzing E5-specific CD8(+) gamma interferon-positive (IFN-gamma(+)) double-positive cells in C57BL/6 mice with flow cytometry. The results showed the region spanning amino acids 25 to 33 (VCLLIRPLL) contained the potential D(b)-restricted CTL epitope. Subsequently, to determine whether peptide E5 25-33-based vaccination could induce E5-specific CTL activity, syngeneic animals received E5 25-33 emulsified with either CpG oligodeoxynucleotide (CpG ODN 1826) or Freund's adjuvant, and the growth of the tumors was monitored. The results showed that although both adjuvants induced E5-specific CD8(+) IFN-gamma(+) T cells and eradicated E5-containing tumor growth, CpG ODN was found to stimulate stronger CTL response than Freund's adjuvant. We also compared the immune response of the effector/memory/recall phase induced by E5 25-33 peptide or by E5 protein that was synthesized in vivo by adenovirus-based E5 gene delivery. E5 25-33 peptide plus CpG ODN was shown to be a superior vaccine compared to the adenovirus-based E5 gene. Interestingly, their chronological patterns of immune response were similar, suggesting that E5 25-33 is a major CTL peptide of E5 protein.
Chen
Yi-Fang
YF
Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Lin
Chih-Wei
CW
Tsao
Yeou-Ping
YP
Chen
Show-Li
SL
D000276:Adjuvants, Immunologic; D000818:Animals; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014611:Vaccination; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D018984:Epitopes, T-Lymphocyte; D009838:Oligodeoxyribonucleotides; D009856:Oncogene Proteins, Viral; D010455:Peptides; D014765:Viral Vaccines; C054304:oncogene protein E5, Bovine papillomavirus type 1