In vivo administration of a lentiviral vaccine targets DCs and induces efficient CD8(+) T cell responses.
The present study evaluates the potential of third-generation lentivirus vectors with respect to their use as in vivo-administered T cell vaccines. We demonstrate that lentivector injection into the footpad of mice transduces DCs that appear in the draining lymph node and in the spleen. In addition, a lentivector vaccine bearing a T cell antigen induced very strong systemic antigen-specific cytotoxic T lymphocyte (CTL) responses in mice. Comparative vaccination performed in two different antigen models demonstrated that in vivo administration of lentivector was superior to transfer of transduced DCs or peptide/adjuvant vaccination in terms of both amplitude and longevity of the CTL response. Our data suggest that a decisive factor for efficient T cell priming by lentivector might be the targeting of DCs in situ and their subsequent migration to secondary lymphoid organs. The combination of performance, ease of application, and absence of pre-existing immunity in humans make lentivector-based vaccines an attractive candidate for cancer immunotherapy.
Esslinger
Christoph
C
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland. christoph.esslinger@isrec.unil.ch
Chapatte
Laurence
L
Finke
Daniela
D
Miconnet
Isabelle
I
Guillaume
Philippe
P
Lévy
Frédéric
F
MacDonald
H Robson
HR
D000818:Animals; D000951:Antigens, Neoplasm; D001853:Bone Marrow / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement; D002474:Cell-Free System; D018899:CpG Islands; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins; D006801:Humans; D007167:Immunotherapy; D016086:Lentivirus / Q000235:genetics*; D008164:Luminescent Proteins / Q000378:metabolism; D058965:MART-1 Antigen; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D009363:Neoplasm Proteins / Q000494:pharmacology; D009841:Oligonucleotides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors; D014612:Vaccines / Q000008:administration & dosage*
D000951:Antigens, Neoplasm; D000939:Epitopes; D008164:Luminescent Proteins; D058965:MART-1 Antigen; C548667:MLANA protein, human; C548668:Mlana protein, mouse; D009363:Neoplasm Proteins; D009841:Oligonucleotides; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D014612:Vaccines; D049452:Green Fluorescent Proteins