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Journal of Virology, March 2000, p. 2888-2894, Vol. 74, No. 6
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Recombinant Adeno-Associated Virus Expressing Human Papillomavirus Type 16 E7 Peptide DNA Fused with Heat Shock Protein DNA as a Potential Vaccine for Cervical Cancer

Dai-Wei Liu,1,2 Yeou-Ping Tsao,1,3 John T. Kung,4 Yu-An Ding,5 Huey-Kang Sytwu,1 Xiao Xiao,6 and Show-Li Chen1,*

Department of Microbiology and Immunology1 and the Graduate Institute of Medical Science,2 National Defense Medical Center, Institute of Molecular Biology, Academia Sinica,4 and Division of Cardiology, Veterans General Hospital,5 Taipei, and Department of Ophthalmology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan,3 Taiwan, Republic of China, and Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, Pennsylvania6

Received 7 October 1999/Accepted 7 December 1999

In this study, we explore a potential vaccine for human papillomavirus (HPV)-induced tumors, using heat shock protein as an adjuvant, a peptide vaccine for safety, and adeno-associated virus (AAV) as a gene delivery vector. The tumor vaccine was devised by constructing a chimeric gene which contained HPV type 16 E7 cytotoxic T-lymphocyte (CTL) epitope DNA (M. C. Feltkamp, H. L. Smits, M. P. Vierboom, R. P. Minnaar, B. M. de Jongh, J. W. Drijfhout, J. ter Schegget, C. J. Melief, and W. M. Kast, Eur. J. Immunol. 23:2242-2249, 1993) fused with the heat shock protein gene as a tumor vaccine delivered via AAV. Our results demonstrate that this vaccine can eliminate tumor cells in syngeneic animals and induce CD4- and CD8-dependent CTL activity in vitro. Moreover, studies with knockout mice with distinct T-cell deficiencies confirm that CTL-induced tumor protection is CD4 and CD8 dependent. Taken together, the evidence indicates that this chimeric gene delivered by AAV has potential as a cervical cancer vaccine.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, Republic of China. Phone: 886-2-87923100, ext. 18543. Fax: 886-2-23687806. E-mail: yptsao{at}mail.ht.net.tw.

Journal of Virology, March 2000, p. 2888-2894, Vol. 74, No. 6
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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