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Therapeutic efficacy of vesicular stomatitis virus-based E6 vaccination in rabbits
Janet L Brandsma1, Mark Shlyankevich, Linda Buonocore
1Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520-8016, USA. janet.brandsma@yale.edu
Abstract:
Millions of people worldwide are currently infected with human papillomaviruses (HPVs). A therapeutic HPV vaccine would have widespread applicability because HPV-associated lesions are difficult to treat and may progress to carcinoma. We developed three attenuated VSV recombinants expressing the cottontail rabbit papillomavirus (CRPV) early protein E6 for use as vaccines. In cultured cells, two vectors expressed different levels of the E6 protein, and one expressed a ubiquitin-E6 fusion protein. All three were tested for therapeutic efficacy in the cottontail rabbit papillomavirus (CRPV)-rabbit model. Mock vaccination had no effect on papilloma growth. In contrast, inoculation with any of the VSV-E6 vaccines reduced the rate of papilloma growth to as little as 24% the rate in the controls. In five experiments, these effects were achieved after a single immunization. Furthermore, complete papilloma regression occurred in some rabbits observed for 4 months. A VSV-based papillomavirus E6 vaccine could have significant advantages over other therapeutic HPV vaccine candidates described to date.
Insights
A novel therapeutic vaccine using vesicular stomatitis virus (VSV) expressing human papillomavirus (HPV) E6 protein shows promise. This VSV-E6 vaccine effectively reduced papilloma growth and induced regression in a rabbit model.
Area of Science:
- Virology
- Immunology
- Oncology
Background:
- Human papillomaviruses (HPVs) cause widespread infections, with associated lesions potentially progressing to carcinoma.
- Current treatments for HPV-associated lesions are often difficult and ineffective.
- A therapeutic HPV vaccine could address a significant global health need.
Purpose of the Study:
- To develop and evaluate a novel therapeutic vaccine for human papillomavirus (HPV) infections.
- To assess the efficacy of vesicular stomatitis virus (VSV)-based vectors expressing the HPV early protein E6.
- To determine if VSV-E6 vaccines can reduce papilloma growth and induce regression.
Main Methods:
- Development of three attenuated VSV recombinants expressing the cottontail rabbit papillomavirus (CRPV) early protein E6.
- Testing of VSV-E6 vaccines in the CRPV-rabbit model for therapeutic efficacy.
- Evaluation of papilloma growth rate and regression following single immunization.
Main Results:
- VSV-E6 vaccines significantly reduced papilloma growth rates, with some reduced to 24% of control rates.
- A single immunization with VSV-E6 vaccines was sufficient to achieve therapeutic effects.
- Complete papilloma regression was observed in some rabbits within 4 months post-vaccination.
Conclusions:
- VSV-based papillomavirus E6 vaccines demonstrate significant therapeutic potential against HPV-associated lesions.
- This approach offers potential advantages over existing therapeutic HPV vaccine candidates.
- Further development of VSV-E6 vaccines could provide a valuable new strategy for HPV treatment.
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