Engineered lentivector targeting of dendritic cells for in vivo immunization
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.
Additional Information
© 2008 Nature Publishing Group. Received 15 June 2007. Accepted 07 February 2008. Published 24 February 2008. 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. Lili Yang and Haiguang Yang: These authors contributed equally to this work. Author Contributions: L.Y. and H.Y. designed research, performed experiments, discussed the results, wrote the paper. K.R., T.C., K.J., L.Z., A.E., A.W., D.Y. performed experiments. D.B. designed research, discussed the results, wrote the paper and provided financial support. P.W. designed research, performed experiments, discussed results, wrote the paper, provided financial support and coordinated the whole project.Attached Files
Accepted Version - nihms44518.pdf
Supplemental Material - 41587_2008_BFnbt1390_MOESM14_ESM.pdf
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41587_2008_BFnbt1390_MOESM14_ESM.pdf
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Additional details
Identifiers
- PMCID
- PMC2366162
- Eprint ID
- 102621
- Resolver ID
- CaltechAUTHORS:20200417-142716949
Funding
- NIH
- R01AI068978
- Bill and Melinda Gates Foundation
- Skirball Foundation
Dates
- Created
-
2020-04-20Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field