DNA vaccine with alpha -galactosylceramide at prime phase enhances anti-tumor immunity after boosting with antigen-expressing dendritic cells.

摘要

DNA vaccines contribute to a promising new approach for the generation of cytotoxic T lymphocytes (CTL). DNA vaccines do have several disadvantages, including poor immunogenicity and oncogene expression. We used the natural killer T-cell (NKT) ligand alpha -galactosylceramide ( alpha -GalCer) as an adjuvant to prime initial DNA vaccination; and used the potent immune-stimulatory tumor antigen-expressing dendritic cells (DCs) as a booster vaccination. A DNA vaccine expressing human papillomavirus (HPV) type 16 E7 (pcDNA3-CRT/E7) was combined with alpha -GalCer at the prime phase, and generated a higher number of E7-specific CD8+ T-cells in vaccinated mice than vaccine used at boost phase. Therefore, priming with a DNA vaccine in the presence of alpha -GalCer and boosting with E7-pulsed DC-1 led to a significant enhancement of E7-specific CD8+ effector and memory T-cells as well as significantly improved therapeutic and preventive effects against an E7-expressing tumor model (TC-1) in vaccinated mice. Our findings suggested that the potency of a DNA vaccine combined with alpha -GalCer could be further enhanced by boosting with an antigen-expressing DC-based vaccine to generate anti-tumor immunity.Digital Object Identifier http://dx.doi.org/10.1016/j.vaccine.2010.08.079