Boosting anti-idiotype immune response with recombinant AAV enhances tumour protection induced by gene gun vaccination

Abstract

Thanks to the safety of administration, efficiency of in vivo transduction and persistence of transgene expression, vectors based on the adeno-associated virus (AAV) are extensively utilized in both preclinical and clinical experimentation. Here we thoroughly explore the potential of AAV-mediated antigen delivery for tumour vaccination. A recombinant AAV vector (rAAV) encoding a lymphoma idiotype (Id) in a single-chain variable fragment format was found to induce an efficient anti-Id immune response upon injection in immunocompetent animals. The intensity of the immune response and the protective effect of rAAV administration in vivo were systematically compared with those elicited by simple injection of naked DNA or biolistic immunization. The results indicate that Id delivery via rAAV enhances the intensity of immune response compared with injection of naked DNA, while anti-idiotypic antibodies titres are not considerably increased compared with biolistic vaccination. On the contrary, a prime-boost vaccination strategy combining biolistic and AAV DNA delivery results in a major increase in anti-Id antibody response compared with the repetitive biolistic immunization. This increased anti-Id humoral response strictly correlated with a significant improvement on tumour protection in vivo. © 2008 The Authors.