Prime-boost therapeutic vaccination in mice with DNA/DNA or DNA/Fowlpox virus recombinants expressing the Human Papilloma Virus type 16 E6 and E7 mutated proteins fused to the coat protein of Potato virus X.
The therapeutic antitumor potency of a prime-boost vaccination strategy was explored, based on the mutated, nontransforming forms of the E6 (E6F47R) and E7 (E7GGG) oncogenes of Human Papilloma Virus type 16 (HPV16), fused to the Potato virus X (PVX) coat protein (CP) sequence. Previous data showed that CP fusion improves the immunogenicity of tumor-associated antigens and may thus increase their efficacy. After verifying the correct expression of E6F47RCP and E7GGGCP inserted into DNA and Fowlpox virus recombinants by Western blotting and immunofluorescence, their combined use was evaluated for therapy in a pre-clinical mouse model of HPV16-related tumorigenicity. Immunization protocols were applied using homologous (DNA/DNA) or heterologous (DNA/Fowlpox) prime-boost vaccine regimens. The humoral immune responses were determined by ELISA, and the therapeutic efficacy evaluated by the delay in tumor appearance and reduced tumor volume after inoculation of syngeneic TC-1* tumor cells. Homologous DNA/DNA genetic vaccines were able to better delay tumor appearance and inhibit tumor growth when DNAE6F47RCP and DNAE7GGGCP were administered in combination. However, the heterologous DNA/Fowlpox vaccination strategy was able to delay tumor appearance in a higher number of animals when E6F47RCP and in particular E7GGGCP were administered alone.
Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. Electronic address: elena.illiano@unimi.it.
Elena
E
Illiano
Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. Electronic address: massimiliano.bissa@unimi.it.
Massimiliano
M
Bissa
Laboratory of Virology HPV-UNIT, Regina Elena National Cancer Institute, Rome, Italy. Electronic address: francesca.paolini@ifo.gov.it.
Francesca
F
Paolini
Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy. Electronic address: carlo.zanotto@unimi.it.
Carlo
C
Zanotto
Cellular and Molecular Pharmacology Section, CNR Institute of Neurosciences, University of Milan, Milan, Italy; Catholic University "Our Lady of Good Counsel", Tirana, Albania. Electronic address: carlo.degiulimorghen@unimi.it.
Carlo
C
De Giuli Morghen
Laboratory of Biomedical Technologies, Division of Health Protection Technologies, Department for Sustainability, Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), Casaccia Research Centre, Rome, Italy. Electronic address: rosella.franconi@enea.it.
Rosella
R
Franconi
Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; Cellular and Molecular Pharmacology Section, CNR Institute of Neurosciences, University of Milan, Milan, Italy. Electronic address: antonia.radaelli@unimi.it.
Antonia
A
Radaelli
Laboratory of Virology HPV-UNIT, Regina Elena National Cancer Institute, Rome, Italy. Electronic address: aldo.venuti@ifo.gov.it.
Aldo
A
Venuti
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D005587:Fowlpox virus / Q000235:genetics*; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D007114:Immunization; D007117:Immunization, Secondary; D051379:Mice; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000276:immunology*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
D019496:Cancer Vaccines; D036022:Capsid Proteins; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D019444:Vaccines, DNA; C064366:coat protein, Potato virus S; C059731:oncogene protein E7, Human papillomavirus type 16
E6 and E7 modified oncoproteins; Fowlpox virus recombinants; HPV therapeutic vaccines; Potato virus X coat protein; Prime/boost immunizations