Abstract
Peptide-based vaccines derived from the E7 protein of human papillomavirus (HPV) type 16 were developed to induce effective T cell responses against established cervical cancer, but have met with limited clinical success. It is necessary to develop novel peptide-based strategies to substantially improve the immune response against HPV16-related cancer. In this study, we aimed to design a novel peptide-based self-assembled nanoparticle HPV16 vaccine by combining the cell-penetrating peptide HIV-1 Tat(49-57) that was fused with the HPV16 E7(49-57) cytotoxic T lymphocyte (CTL) epitope and the granulocyte-macrophage colony stimulating factor (GM-CSF) gene, and to investigate how it improves the immune response and the therapeutic outcome ex vivo and in vivo. Nanoparticles were prepared and identified by transmission electron microscopy (TEM), gel retardation and DNase I protection assays. This type of vaccine formulation formed the 20-80 nm nanoparticles, and greatly improved epitope-specific immunity both ex vivo and in vivo. Importantly, this vaccine type was associated with decreased tumor growth and enhanced long-term survival in the prophylactic and therapeutic mouse models. The underlying mechanisms were determined to involve priming of enhanced frequency of CD8(+) memory T subtype cells. These results suggest that the nanoparticle Tat-E7/pGM-CSF represents a promising novel approach to enhance the potency of peptide-based cervical cancer vaccines, and this vaccine design strategy may act as a useful reference for research of virus-associated diseases and specific tumor immunotherapies.