Immunization with a lentivector that targets tumor antigen expression to dendritic cells induces potent CD8+ and CD4+ T-cell responses.
Lentivectors stimulate potent immune responses to antigen transgenes and are being developed as novel genetic vaccines. To improve safety while retaining efficacy, we constructed a lentivector in which transgene expression was restricted to antigen-presenting cells using the mouse dectin-2 gene promoter. This lentivector expressed a green fluorescent protein (GFP) transgene in mouse bone marrow-derived dendritic cell cultures and in human skin-derived Langerhans and dermal dendritic cells. In mice GFP expression was detected in splenic dectin-2(+) cells after intravenous injection and in CD11c(+) dendritic cells in the draining lymph node after subcutaneous injection. A dectin-2 lentivector encoding the human melanoma antigen NY-ESO-1 primed an NY-ESO-1-specific CD8(+) T-cell response in HLA-A2 transgenic mice and stimulated a CD4(+) T-cell response to a newly identified NY-ESO-1 epitope presented by H2 I-A(b). As immunization with the optimal dose of the dectin-2 lentivector was similar to that stimulated by a lentivector containing a strong constitutive viral promoter, targeting antigen expression to dendritic cells can provide a safe and effective vaccine.
Lopes
Luciene
L
Division of Infection and Immunity, University College London, Windeyer Building, 46 Cleveland Street, London W1T 4JF, United Kingdom.
Dewannieux
Marie
M
Gileadi
Uzi
U
Bailey
Ranbir
R
Ikeda
Yasuhiro
Y
Whittaker
Christopher
C
Collin
Matthew P
MP
Cerundolo
Vincenzo
V
Tomihari
Mizuki
M
Ariizumi
Kiyoshi
K
Collins
Mary K
MK
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000276:immunology*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics; D016086:Lentivirus / Q000235:genetics / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D013154:Spleen / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D000939:Epitopes; D037181:Lectins, C-Type; D008565:Membrane Proteins; D014765:Viral Vaccines; C445340:dectin-2, mouse; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins