Fusion of Glioblastoma Tumor Antigens to Herpes Simplex Virus-1 Glycoprotein D Enhances Secondary Adaptive Immune Responses in a DNA Vaccine Strategy

Rios WM, De Molfetta JB, Brandão IT, Masson AP, Peripato R, Silva ID, Rodrigues RF, Arnoldi F, De Souza PRM, Diniz MDO, Ferreira LCDS and Silva CL

Glioblastoma multiforme (GBM) is a recurrent and fatal cancer. EGFRvIII, MAGE-3 and GLEA-2 are antigens that are found in this highly heterogeneous tumor and that are absent in normal tissue. Usually, conventional GMB treatments do not prevent recurrence, reinforcing the need for new therapeutic strategies. Vaccination can be an alternative GMB therapy capable to induce long-lasting and specific immune responses to tumors antigens but requires the activation of strong cellular responses. Fusion of tumor antigens with microbial-derived proteins is a rather simple approach that can enhance the immunogenicity of vaccines, particularly, DNA vaccines. In this study, we constructed DNA vaccines encoding GBM tumor antigens fused to glycoprotein D from herpes simplex virus-1 and evaluated their immunogenicity in C57BL/6 mice. The tumor antigens were correctly expressed by the DNA vaccines and induced cell mediated immune responses under experimental conditions. The vaccines encoding antigens genetically fused with gD induced higher cellular immune responses, associated with IFN-γ and IL-10 production, than vaccines encoding non-fused GMB antigens. Therefore, DNA vaccinations induced a Th1-biased immune response. We concluded that the strategy could be an effective immunotherapeutic approach for GBM.