HIV-1 Gag-specific immunity induced by a lentivector-based vaccine directed to dendritic cells |
| |
| Authors: | Bingbing Dai Lili Yang Haiguang Yang Biliang Hu David Baltimore Pin Wang |
| |
| Affiliation: | aMork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA 90089; and ;bDivision of Biology, California Institute of Technology, Pasadena, CA 91125 |
| |
| Abstract: | Lentivectors (LVs) have attracted considerable interest for their potential as a vaccine delivery vehicle. In this study, we evaluate in mice a dendritic cell (DC)-directed LV system encoding the Gag protein of human immunodeficiency virus (HIV) (LV-Gag) as a potential vaccine for inducing an anti-HIV immune response. The DC-directed specificity is achieved through pseudotyping the vector with an engineered Sindbis virus glycoprotein capable of selectively binding to the DC-SIGN protein. A single immunization by this vector induces a durable HIV Gag-specific immune response. We investigated the antigen-specific immunity and T-cell memory generated by a prime/boost vaccine regimen delivered by either successive LV-Gag injections or a DNA prime/LV-Gag boost protocol. We found that both prime/boost regimens significantly enhance cellular and humoral immune responses. Importantly, 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. These results demonstrate that this DC-directed LV immunization is a potent modality for eliciting anti-HIV immune responses. |
| |
| Keywords: | AIDS vaccine human immunodeficiency virus lentiviral vector T cell vaccine |
|
|
