(568u) Lentivector-Based Vaccine Directed to Dendritic Cells for Gene Delivery of HIV-1 Gag

A desirable feature of AIDS vaccine is the ability to generate immune responses with high potency as well as a broad spectrum. We are developing a lentivirus-based approach that harnesses its potential as a vaccine delivery vehicle. Anti-HIV genetic materials (HIV gag protein) were transported to dendritic cells by pseudotyping the vector with an engineered Sindbis virus glycoprotein, which was capable of selectively binding to the DC-SIGN receptor. We examined the vaccine quality in mice model, and found that a single immunization by this vector induces a durable HIV Gag-specific immune response. We emphasized on prime/boost strategies, and observed enhanced cellular and humoral immune responses from both successive LV-Gag injections and DNA prime/LV-Gag boost protocols. In particular, a heterologous DNA prime/LV-Gag boost regimen results in superior Gag-specific T-cell responses as compared with a DNA prime/adenovector boost immunization. It induces not only a higher magnitude response, as measured by Gag-specific tetramer analysis and intracellular IFN-γ staining, but also a better quality of response evidenced by a wider mix of cytokines produced by the Gag-specific CD8+ and CD4+ T cells. A boosting immunization with LV-Gag also generates T cells reactive to a broader range of Gag-derived epitopes. We suggested that this DC directed LV immunization is a potent gene delivery approach for eliciting anti-HIV immune responses.