Enhancement of DNA vaccine potency by sandwiching antigen-coding gene between XXXX ( @entity13385 ) and IgG Fc fragment genes.

@entity13385 @entity19 @entity1799 @entity5
DNA vaccine has become an attractive approach for generating antigen-specific immunity. Targeting antigens to FcRs for IgG (FcgammaRs) on dendritic cells (DCs) has been demonstrated to enhance antigen presentation. @entity13385 ( @entity13385 ) has been shown to increase immune responses not only by promoting coclustering of T cells and DCs in the lymph nodes and spleen but also by regulating their immunogenic potential for the induction of T cell responses. In this study, using @entity1799 E7 as a model antigen, we constructed a chemotactic-antigen plasmid DNA vaccine (pSLC-E7-Fc) by linking @entity13385 and Fc gene sequences to each end of E7 and evaluated its potency of eliciting specific immune response. We found that immunization with pSLC-E7-Fc generated much stronger E7-specific lymphocyte proliferative and cytotoxic T lymphocyte (CTL) responses than control DNA. All the @entity19 receiving pSLC-E7-Fc prophylactic vaccination remained @entity5 free upon subcutaneous inoculation of @entity19 cells, while those given control DNA all developed @entity5 . These @entity5 -free @entity19 were also protected against TC-1 rechallenge. Complete @entity5 regression with long-term survival occurred in 72% of @entity19 given pSLC-E7-Fc as therapeutic vaccination. In experimental lung metastasis model wherein @entity19 cells were intravenously injected, therapeutic vaccination with pSLC-E7-Fc significantly reduced the number of @entity5 nodules in the lung. In vivo depletion with antibodies against CD4+or CD8+ T cells both resulted in complete abrogation of the pSLC-E7-Fc-induced immunotherapeutic effect. Our data indicate that the DNA vaccine constructed by the fusion of @entity13385 and IgG Fc fragment genes to antigen-coding gene is an effective approach to induce potent anti- @entity5 immune response via both CD4+ and CD8+ T cells dependent pathways.
