Anti-tumor DNA vaccines based on the expression of human papillomavirus-16 E6/E7 oncoproteins genetically fused with the glycoprotein D from herpes simplex virus-1.
DNA vaccines encoding the human papillomavirus type-16 (HPV-16) E6 and E7 oncoproteins genetically fused to the human herpes simplex virus type 1 (HSV-1) gD protein were tested in mice for induction of T cell-mediated immunity and protection against tumor cell challenge. Hybrid genes, generated after insertion of E6 or E7-encoding sequences into internal sites of the gD-encoding gene, were transcribed in vitro and the chimeric proteins were expressed at the surface of in vitro-transfected mammalian cells. Female C57BL/6 mice immunized with 4 intramuscular doses (100 microg of DNA/dose) of the DNA vaccines encoding E7 efficiently generated E7-specific CD8(+) T cells. Vaccination of mice with the DNA vaccines encoding the E7, or both E6 and E7, conferred complete protection to challenges from TC-1 tumor cells and partial therapeutic effect (40%) in mice inoculated with TC-1 cells on the same day or 5 days prior to the first vaccine dose.
Lasaro
Marcio O
MO
Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, SP, 05508-900, Brazil.
Diniz
Mariana O
MO
Reyes-Sandoval
Arturo
A
Ertl
Hildegund C
HC
Ferreira
Luis C S
LC
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D003593:Cytoplasm / Q000737:chemistry; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D018259:Herpesvirus 1, Human / Q000235:genetics; D022283:Herpesvirus Vaccines / Q000235:genetics / Q000276:immunology*; D052162:Human papillomavirus 16 / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000473:pathology / Q000517:prevention & control*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000517:prevention & control; D053918:Papillomavirus Vaccines; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
D016207:Cytokines; C068651:E6 protein, Human papillomavirus type 16; D022283:Herpesvirus Vaccines; D008565:Membrane Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C039447:glycoprotein D, Human herpesvirus 1; C069093:herpes simplex virus-1 glycoprotein D vaccine; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma