Lentiviral Vectors with CMV or MHCII Promoters Administered In Vivo: Immune Reactivity Versus Persistence of Expression
In: Molecular Therapy, Jg. 15 (2007-07-01), S. 1390-1399
Online
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Zugriff:
Lentiviral vectors (LVs) are potential tools for genetic vaccination. To improve the safety of LV vaccines, we evaluated the selectivity, bio-distribution, persistence of expression, and immune potency of vesicular stomatitis virus G (VSV-G)-pseudotyped vectors transcriptionally targeted to antigen presenting cells (APCs) through a major histocompatibility complex class II (MHCII) promoter. Control vectors contained the ubiquitous cytomegalovirus (CMV) promoter. Bio-distribution studies after intravenous injections of LVs expressing green fluorescent protein (GFP) or luciferase were conducted by a combination of flow cytometry, immunofluorescence, real-time quantitative polymerase chain reaction (RT-Q-PCR) and whole-body bioluminescence analyses. GFP-expressing vectors showed selective expression in MHCII(+) cells of spleen and LV-CMV-GFP administration produced noticeable spleen inflammation, whereas LV-MHCII-GFP did not. Long-term optical imaging analyses of C57BL/6 mice injected with LV-CMV-LUC showed diminishing luciferase expression in the liver and spleen over time. Vaccination/boost with LV-CMV expressing the melanoma antigen tyrosinase-related protein 2 (TRP2) yielded dose-dependent antigen-specific CD8(+) T-cell reactivity and high protection against B16 melanoma challenge. Unexpectedly, administration of LVs containing the MHCII promoter resulted in persistence of luciferase expression and viral integration in MHCII(+) splenocytes and virtually no CD8(+) T-cell responses against TRP2. These studies reveal that APC transduction by LVs could lead to immune reactivity (LV-CMV) or persistence of transgene expression (LV-MHCII), providing a relevant paradigm for vaccination and gene replacement approaches.
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Lentiviral Vectors with CMV or MHCII Promoters Administered In Vivo: Immune Reactivity Versus Persistence of Expression
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Autor/in / Beteiligte Person: | Stripecke, Renata ; Prins, Robert M. ; Anselmi, Laura ; Rozengurt, Nora ; Sternini, Catia ; Comin-Anduix, Begonya ; Cui, Yan ; Kasahara, Noriyuki ; Kimura, Takahiro ; Wang, He-Jing ; Faure-Kumar, Emmanuelle ; Koya, Richard C. |
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Zeitschrift: | Molecular Therapy, Jg. 15 (2007-07-01), S. 1390-1399 |
Veröffentlichung: | Elsevier BV, 2007 |
Medientyp: | unknown |
ISSN: | 1525-0016 (print) |
DOI: | 10.1038/sj.mt.6300180 |
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