Engineered lentivector targeting of dendritic cells for in vivo immunization

• Published in: Nature biotechnology 2008-03, Vol.26 (3), p.326-334
• Main Authors: Yang, Lili, Yang, Haiguang, Rideout, Kendra, Cho, Taehoon, Joo, Kye il, Ziegler, Leslie, Elliot, Abigail, Walls, Anthony, Yu, Dongzi, Baltimore, David, Wang, Pin
• Format: Article
• Language: English
• Subjects: Agriculture; Animals; B-Lymphocytes - cytology; B-Lymphocytes - immunology; Bioinformatics; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedicine; Biotechnology; Cancer Vaccines - immunology; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; Cell Adhesion Molecules - metabolism; Cell Line; Cellular biology; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; Genetic aspects; Genetic engineering; Genetic vectors; Genetic Vectors - genetics; Health aspects; Health. Pharmaceutical industry; Humans; Immunization; Immunology; Industrial applications and implications. Economical aspects; Injection; Lectins, C-Type - metabolism; Lentivirus - genetics; Life Sciences; Methods; Mice; Mice, Inbred C57BL; Mice, Transgenic; Miscellaneous; Neoplasms, Experimental - immunology; Neoplasms, Experimental - therapy; Ovalbumin - genetics; Ovalbumin - immunology; Proteins; Receptors, Cell Surface - metabolism; Research methodology; Sensitivity and Specificity; Sindbis virus; Sindbis Virus - genetics; Sindbis Virus - metabolism; Transduction, Genetic; Tumors
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt1390

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.