Abstract
We report a method of inducing antigen production in dendritic cells by in vivo targeting with lentiviral vectors that specifically bind to the dendritic cell-surface protein DC-SIGN. To target dendritic cells, we enveloped the lentivector with a viral glycoprotein from Sindbis virus engineered to be DC-SIGN-specific. In vitro, this lentivector specifically transduced dendritic cells and induced dendritic cell maturation. A high frequency (up to 12%) of ovalbumin (OVA)-specific CD8+ T cells and a significant antibody response were observed 2 weeks after injection of a targeted lentiviral vector encoding an OVA transgene into naive mice. This approach also protected against the growth of OVA-expressing E.G7 tumors and induced regression of established tumors. Thus, lentiviral vectors targeting dendritic cells provide a simple method of producing effective immunity and may provide an alternative route for immunization with protein antigens.
| Original language | English |
|---|---|
| Pages (from-to) | 326-334 |
| Number of pages | 9 |
| Journal | Nature Biotechnology |
| Volume | 26 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2008 |
Bibliographical note
Funding Information:We are grateful to James Strauss for providing reagents and April Tai for a critical reading of the manuscript. This work was supported by a grant from the National Institute of Health (R01AI068978), a grant from the Bill and Melinda Gates Foundation through the Grand Challenges in Global Health Initiative, and by the Skirball Foundation.