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Immunization strategy against cervical cancer involving an alphavirus vector expressing high levels of a stable fusion protein of human papillomavirus 16 E6 and E7

Gene Therapy volume 9, pages 85–94 (2002)Cite this article

Abstract

We are developing immunization strategies against cervical carcinoma and premalignant disease, based on the use of recombinant Semliki Forest virus (SFV) encoding the oncoproteins E6 and E7 from high-risk human papilloma viruses (HPV). Thus far, protein-based, as well as genetic immunization studies have demonstrated low to moderate cellular immune responses against E6 and E7. To improve these responses, we modified the structure and expression level of the E6 and E7 proteins produced by the SFV vector. Specifically, a construct was generated encoding a fusion protein of E6 and E7, while furthermore a translational enhancer was included (enhE6,7). Infection of cells with recombinant SFV-enhE6,7 resulted in the production of large amounts of the E6,7 fusion protein. The fusion protein was more stable than either one of the separate proteins. Immunization of mice with SFV-enhE6,7 resulted in strong, long-lasting HPV-specific cytotoxic T lymphocyte responses. Tumor challenge experiments in mice demonstrated that immunization with SFV-enhE6,7 resulted in prevention of tumor outgrowth and subsequent protection against tumor re-challenge.

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Acknowledgements

We thank Dr AGJ van der Zee, Dr Hollema and Dr P Liljeström for advice and stimulating discussions and B Dontje for expert technical assistance. Part of this work was supported by the EU Biotechnology and Biomedicin and Health programmes.

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Authors and Affiliations

  1. Department of Medical Microbiology, University of Groningen, Molecular Virology Section, Groningen, The Netherlands

    T Daemen, J Regts, M Holtrop & J Wilschut

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  1. T Daemen
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  4. J Wilschut
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Daemen, T., Regts, J., Holtrop, M. et al. Immunization strategy against cervical cancer involving an alphavirus vector expressing high levels of a stable fusion protein of human papillomavirus 16 E6 and E7. Gene Ther 9, 85–94 (2002). https://doi.org/10.1038/sj.gt.3301627

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