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.

ABSTRACT

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.