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.

Persistent expression of biologically active anti-HER2 antibody by AAVrh.10-mediated gene transfer

“…Additionally, the ability of virus vectors to stimulate an immune response against ectopic proteins expressed from the transgene they carry make the immune responses to genetic delivered antibodies more likely47. With adenovirus as a platform, high levels of circulating ectopic monoclonal antibodies was obtained following in vivo gene transfer without inducing an anti-idiotype response sufficiently robust to exert a neutralizing effect32.…”

Prevention of Arthritis by Locally Synthesized Recombinant Antibody Neutralizing Complement Component C5

“…However, potential insertion of viral DNA into the cell genome and formation of antibodies to viral proteins, which may reduce viral persistence and limit the transfection efficiency, represent two major drawbacks of this technical approach [19], [30], [31].…”

Adeno-associated virus (AAV) vectors in cancer gene therapy

“…AAV2 encoding a B-cell leukemia/lymphoma 1 (BCL1) idiotype led to the generation of anti-Id antibodies and protection against BCL1 cell-based tumors [173]. Intramuscular AAV2 packaged with the LMP2/1-hsp fusion gene, consisting of the Epstein-Barr virus latent membrane proteins 1 and 2 fused to heat shock protein as an adjuvant, to a tumor model based on SP2/0 cells expressing LMP2 led to a humoral and CTL response against LMP2-expressing tumor cells, 83% reduction in tumor growth, and long-term survival of 90% of treated animals [174].…”