Enhanced anti-tumor effect of a gene gun-delivered DNA vaccine encoding the human papillomavirus type 16 oncoproteins genetically fused to the herpes simplex virus glycoprotein D

• Published in: Brazilian journal of medical and biological research Vol. 44; no. 5; pp. 421 - 427
• Main Authors: Diniz, M O, Ferreira, L C S
• Format: Journal Article
• Language: English
• Published: Brazil Associação Brasileira de Divulgação Científica 01.05.2011
• Subjects: Animals; Anti-cancer vaccine; Cancer Vaccines - administration & dosage; Cancer Vaccines - genetics; Cancer Vaccines - immunology; CD8-Positive T-Lymphocytes - immunology; DNA vaccine; Female; Gene gun; HPV-16; Human papillomavirus 16 - genetics; Human papillomavirus 16 - immunology; Injections, Intradermal; Mice; Mice, Inbred C57BL; Neoplasms, Experimental - immunology; Neoplasms, Experimental - prevention & control; Oncogene Proteins, Viral - genetics; Oncogene Proteins, Viral - immunology; Simplexvirus - genetics; Simplexvirus - immunology; Vaccines, DNA - administration & dosage; Vaccines, DNA - genetics; Vaccines, DNA - immunology; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology
• ISSN: 1414-431X; 1414-431X
• DOI: 10.1590/S0100-879X2011000500007

Anti-cancer DNA vaccines have attracted growing interest as a simple and non-invasive method for both the treatment and prevention of tumors induced by human papillomaviruses. Nonetheless, the low immunogenicity of parenterally administered vaccines, particularly regarding the activation of cytotoxic CD8+ T cell responses, suggests that further improvements in both vaccine composition and administration routes are still required. In the present study, we report the immune responses and anti-tumor effects of a DNA vaccine (pgD-E7E6E5) expressing three proteins (E7, E6, and E5) of the human papillomavirus type 16 genetically fused to the glycoprotein D of the human herpes simplex virus type 1, which was administered to mice by the intradermal (id) route using a gene gun. A single id dose of pgD-E7E6E5 (2 µg/dose) induced a strong activation of E7-specific interferon-γ (INF-γ)-producing CD8+ T cells and full prophylactic anti-tumor effects in the vaccinated mice. Three vaccine doses inhibited tumor growth in 70% of the mice with established tumors. In addition, a single vaccine dose consisting of the co-administration of pgD-E7E6E5 and the vector encoding interleukin-12 or granulocyte-macrophage colony-stimulating factor further enhanced the therapeutic anti-tumor effects and conferred protection to 60 and 50% of the vaccinated mice, respectively. In conclusion, id administration of pgD-E7E6E5 significantly enhanced the immunogenicity and anti-tumor effects of the DNA vaccine, representing a promising administration route for future clinical trials.