Engineered lentivector targeting of dendritic cells for in vivo immunization.
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.
Yang
Lili
L
Division of Biology, California Institute of Technology, 1200 E. California Blvd, Pasadena, California 91125, USA.
Yang
Haiguang
H
Rideout
Kendra
K
Cho
Taehoon
T
Joo
Kye Il
KI
Ziegler
Leslie
L
Elliot
Abigail
A
Walls
Anthony
A
Yu
Dongzi
D
Baltimore
David
D
Wang
Pin
P
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D011956:Receptors, Cell Surface / Q000378:metabolism; D012680:Sensitivity and Specificity; D012845:Sindbis Virus / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D019496:Cancer Vaccines; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D010047:Ovalbumin; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin