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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
CD8-Positive T-Lymphocytes / immunology
-
Cytokines / analysis
-
Cytoplasm / chemistry
-
Disease Models, Animal
-
Female
-
Flow Cytometry
-
Herpesvirus 1, Human / genetics
-
Herpesvirus Vaccines / genetics
-
Herpesvirus Vaccines / immunology*
-
Human papillomavirus 16 / genetics
-
Humans
-
Interferon-gamma / analysis
-
Membrane Proteins / analysis
-
Mice
-
Mice, Inbred BALB C
-
Mice, Inbred C57BL
-
Neoplasms, Experimental / pathology
-
Neoplasms, Experimental / prevention & control*
-
Oncogene Proteins, Viral / genetics
-
Oncogene Proteins, Viral / immunology*
-
Papillomavirus E7 Proteins
-
Papillomavirus Infections / prevention & control
-
Papillomavirus Vaccines*
-
Recombinant Fusion Proteins / genetics
-
Recombinant Fusion Proteins / immunology
-
Repressor Proteins / genetics
-
Repressor Proteins / immunology*
-
Vaccines, DNA / genetics
-
Vaccines, DNA / immunology*
-
Viral Envelope Proteins / genetics
-
Viral Envelope Proteins / immunology*
-
Viral Vaccines / genetics
-
Viral Vaccines / immunology*
Substances
-
Cytokines
-
E6 protein, Human papillomavirus type 16
-
Herpesvirus Vaccines
-
Membrane Proteins
-
Oncogene Proteins, Viral
-
Papillomavirus E7 Proteins
-
Papillomavirus Vaccines
-
Recombinant Fusion Proteins
-
Repressor Proteins
-
Vaccines, DNA
-
Viral Envelope Proteins
-
Viral Vaccines
-
glycoprotein D, Human herpesvirus 1
-
herpes simplex virus-1 glycoprotein D vaccine
-
oncogene protein E7, Human papillomavirus type 16
-
Interferon-gamma