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Journal of Virology, February 2004, p. 1333-1343, Vol. 78, No. 3
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.3.1333-1343.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Cytotoxic-T-Lymphocyte Human Papillomavirus Type 16 E5 Peptide with CpG-Oligodeoxynucleotide Can Eliminate Tumor Growth in C57BL/6 Mice

Yi-Fang Chen,¹ Chih-Wei Lin,¹ Yeou-Ping Tsao,² and Show-Li Chen^1*

Department of Microbiology and Immunology, National Defense Medical Center, Taipei,¹ Department of Ophthalmology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, Republic of China²

Received 6 August 2003/ Accepted 20 October 2003

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-⁺) 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-⁺ 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.

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* Corresponding author. Mailing address: Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, Republic of China. Phone: 886-2-87924895. Fax: 886-2-87924885. E-mail: yptsaoslc{at}yahoo.com.tw.

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Journal of Virology, February 2004, p. 1333-1343, Vol. 78, No. 3
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.3.1333-1343.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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