In vivo administration of a lentiviral vaccine targets DCs and induces efficient CD8+ T cell responses
Christoph Esslinger, … , Frédéric Lévy, H. Robson MacDonald
Christoph Esslinger, … , Frédéric Lévy, H. Robson MacDonald
Published June 1, 2003
Citation Information: J Clin Invest. 2003;111(11):1673-1681. https://doi.org/10.1172/JCI17098.
View: Text | PDF
Article Oncology

In vivo administration of a lentiviral vaccine targets DCs and induces efficient CD8+ T cell responses

Abstract

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.

Authors

Christoph Esslinger, Laurence Chapatte, Daniela Finke, Isabelle Miconnet, Philippe Guillaume, Frédéric Lévy, H. Robson MacDonald

×

Figure 1

Options: View larger image (or click on image) Download as PowerPoint
Tissue distribution of lentivector obtained after in vivo administration...
Tissue distribution of lentivector obtained after in vivo administration into footpads of mice. (a) Detection of integrated lentivector at the site of injection (foot), the draining lymph node, and the spleen but not in the mandibular lymph node and the tip of the tail. Vector integration was detected by amplification of vector-derived GFP sequence with specific primers (arrows) using seminested PCR. dLN, draining lymph node; spl, spleen; man, mandibular lymph node. (b) Histological analysis of GFP expression after administration of lentivector into one hind footpad. The upper panel shows GFP fluorescence of frozen sections of popliteal lymph nodes 2.5 days after injection of CMV-GFP lentivector (lvGFP) or PBS (nontreated) into the footpad. The contralateral popliteal lymph node (contra) of a treated mouse is also shown. Magnification, ×100. The lower panel shows double immunofluorescence analysis of draining lymph nodes and spleen 2.5 days after injection of CMV-GFP lentivector using anti-GFP antibodies (green) counterstained with anti-CD11c, anti-CD11b, and anti-B220 antibodies (red). Magnification, ×400. The use of a CMV-GFP lentivector for immunofluorescence was necessary, because with the bicistronic vaccine constructs (antigen-IRES-GFP), GFP fluorescence was too low to be picked up in histology. For PCR analysis of the GFP sequence, the actual vaccine vector was used.