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Journal of Virology, June 2007, p. 5749-5758, Vol. 81, No. 11
0022-538X/07/$08.00+0     doi:10.1128/JVI.02835-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Vesicular Stomatitis Virus-Based Therapeutic Vaccination Targeted to the E1, E2, E6, and E7 Proteins of Cottontail Rabbit Papillomavirus

Section of Comparative Medicine,¹ Department of Pathology,² Yale Cancer Center,³ Yale Skin Disease Research Center,⁴ Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520⁵

Received 4 January 2007/ Accepted 12 March 2007

Persistent human papillomavirus (HPV)-associated benign and malignant lesions are a major cause of morbidity and mortality worldwide. Vaccination against HPV early proteins could provide an effective means of treating individuals with established infections. Recombinant vesicular stomatitis virus (VSV) vectors have been used previously to elicit strong humoral and cellular immune responses and develop prophylactic vaccines. We have shown that VSV vectors also can be used to elicit therapeutic immunity in the cottontail rabbit papillomavirus (CRPV)-rabbit model of high-risk HPV infection. In the present study, three new VSV vectors expressing the CRPV E1, E2, or E7 protein were produced and compared to the previously generated VSV-E6 vector for therapeutic efficacy. To determine whether vaccine efficacy could be augmented by simultaneous vaccination against two CRPV proteins, the four vaccines were delivered individually and in all possible pairings to rabbits 1 week after CRPV infection. Control rabbits received the recombinant wild-type VSV vector or medium only. Cumulative papilloma volumes were computed for analysis of the data. The analyses showed that VSV-based vaccination against the E1, E2, E6, or E7 protein significantly reduced papilloma volumes relative to those of the controls. Furthermore, VSV-based CRPV vaccination cured all of the papillomas in 5 of 30 rabbits. Of the individual vaccines, VSV-E7 was the most effective. The VSV-E7 vaccine alone was the most effective, as it reduced cumulative papilloma volumes by 96.9% overall, relative to those of the controls, and ultimately eliminated all of the disease in all of the vaccinees. Vaccine pairing was not, however, found to be beneficial, suggesting antigenic competition between the coexpressed CRPV proteins. These preclinical results, obtained in a physiologically relevant animal model of HPV infection, demonstrate that VSV vectors deserve serious consideration for further development as therapeutic antitumor vaccines.

Published ahead of print on 28 March 2007.

This article has been cited by other articles:

• Liao, J. B., Publicover, J., Rose, J. K., DiMaio, D. (2008). Single-Dose, Therapeutic Vaccination of Mice with Vesicular Stomatitis Virus Expressing Human Papillomavirus Type 16 E7 Protein. CVI 15: 817-824 [Abstract] [Full Text]