A prime/boost strategy by DNA/fowlpox recombinants expressing a mutant E7 protein for the immunotherapy of HPV-associated cancers.

Abstract

Development of effective therapeutic vaccines against human papilloma virus (HPV) infections remains a priority, considering the high number of new cases of cervical cancer each year by high-risk HPVs, in particular by HPV-16. Vaccines expressing the E7 oncoprotein, which is detectable in all HPV-positive pre-cancerous and cancer cells, might clear already established tumors and support the treatment of HPV-related lesions. In this study, DNA or fowlpox virus recombinants expressing the harmless variant E7GGG of the HPV-16 E7 oncoprotein (DNA(E7GGG) and FP(E7GGG)) were generated. Two immunization regimens were tested in a pre-clinical mouse model by homologous (FP/FP) or heterologous (DNA/FP) prime-boost protocols to evaluate the immune response and therapeutic efficacy of the proposed HPV-16 vaccine. Low levels of anti-E7-specific antibodies were elicited after immunization, and in vivo experiments resulted in a higher number of tumor-free mice after the heterologous immunization. These results establish a preliminary indication for therapy of HPV-related tumors by the combined use of DNA and avipox recombinants, which might represent safer immunogens than vaccinia-based vaccines.

• Authors: Antonia Radaelli, Carlo De Giuli Morghen, Carlo Zanotto, Sole Pacchioni, Massimiliano Bissa, Rosella Franconi, Silvia Massa, Francesca Paolini, Antonio Muller, Aldo Venuti
• Journal: Virus research (Virus Res) Vol. 170 Issue 1-2 Pg. 44-52 (Dec 2012) ISSN: 1872-7492 [Electronic] Netherlands
• PMID: 22951311 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Cancer Vaccines
• Mutant Proteins
• Papillomavirus E7 Proteins
• Papillomavirus Vaccines
• Vaccines, DNA

Topics

• Animals
• Cancer Vaccines (genetics, immunology, therapeutic use)
• Cell Line
• Female
• Fowlpox virus (genetics)
• Gene Expression
• Human papillomavirus 16 (genetics, immunology)
• Humans
• Immunity, Cellular
• Immunity, Humoral
• Immunization Schedule
• Immunotherapy
• Mice
• Mutant Proteins (immunology)
• Neoplasms (immunology, therapy, virology)
• Papillomavirus E7 Proteins (genetics, immunology)
• Papillomavirus Vaccines (genetics, therapeutic use)
• Plasmids (genetics)
• Transgenes
• Vaccines, DNA (therapeutic use)