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Journal of Virology, January 2004, p. 116-123, Vol. 78, No. 1
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.1.116-123.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Vaccination of Rabbits with an Adenovirus Vector Expressing the Papillomavirus E2 Protein Leads to Clearance of Papillomas and Infection

Janet L. Brandsma,1,2,3,4* Mark Shlyankevich,1 Lixin Zhang,5 Martin D. Slade,6 Edward C. Goodwin,4,7 Woei Peh,8 and Albert B. Deisseroth4,5,{dagger}

Section of Comparative Medicine,1 Department of Pathology,2 Yale Skin Diseases Research Center,3 Yale Comprehensive Cancer Center,4 Section of Medical Oncology,5 Department of Epidemiology and Public Health,6 Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520,7 National Institute for Medical Research, London, England NW7 1AA8

Received 9 July 2003/ Accepted 18 September 2003

Cervical cancer arises from lesions caused by infection with high-risk types of human papillomavirus (HPV). Therefore, vaccination against HPV could prevent carcinogenesis by preventing HPV infection or inducing lesion regression. HPV E2 protein is an attractive candidate for vaccine development because it is required for papilloma formation, is involved in all stages of the virus life cycle, and is expressed in all premalignant lesions as well as some cancers. This study reports vaccination against E2 protein using a rabbit model of papillomavirus infection. A recombinant adenovirus (Ad) vector expressing the E2 protein of cottontail rabbit papillomavirus (CRPV) was tested for therapeutic efficacy in CRPV-infected rabbits. Primary immunization with the Ad-E2 vaccine, compared to immunization with a control Ad vector, reduced the number of papilloma-forming sites from 17 of 45 to 4 of 45. After booster immunization, vaccinated rabbits formed no new papillomas versus an additional 23 papillomas in rabbits that received the control vector. Papillomas in the Ad-E2 vaccinees were significantly smaller than those in the control rabbits, and all four papillomas in the Ad-E2 vaccinated rabbits regressed. No CRPV DNA was detected either in the regression sites or in sites that did not form papillomas, indicating that the vaccination led to clearance of CRPV from all infected sites.

* Corresponding author. Mailing address: Section of Comparative Medicine, Yale University School of Medicine, P.O. Box 208016, New Haven, CT 06520-8016. Phone: (203) 785-4401. Fax: (203) 785-7499. E-mail: janet.brandsma{at}yale.edu.

{dagger} Present address: Sidney Kimmel Cancer Center, San Diego, Calif.

Journal of Virology, January 2004, p. 116-123, Vol. 78, No. 1
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.1.116-123.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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