Lentiviral vectors with CMV or MHCII promoters administered in vivo

Immune reactivity versus persistence of expression

Takahiro Kimura, Richard C. Koya, Laura Anselmi, Catia Sternini, He Jing Wang, Begonya Comin-Anduix, Robert M. Prins, Emmanuelle Faure-Kumar, Nora Rozengurt, Yan Cui, Noriyuki Kasahara, Renata Stripecke

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1390-1399
Number of pages10
JournalMolecular Therapy
Volume15
Issue number7
DOIs
StatePublished - Jul 1 2007
Externally publishedYes

Fingerprint

Major Histocompatibility Complex
Cytomegalovirus
Green Fluorescent Proteins
Luciferases
Vaccination
Spleen
Antigen-Presenting Cells
Virus Integration
CD8 Antigens
Melanoma-Specific Antigens
T-Lymphocytes
Vesicular Stomatitis
Experimental Melanomas
Optical Imaging
Transgenes
Inbred C57BL Mouse
Intravenous Injections
Fluorescent Antibody Technique
Real-Time Polymerase Chain Reaction
Flow Cytometry

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Kimura, T., Koya, R. C., Anselmi, L., Sternini, C., Wang, H. J., Comin-Anduix, B., ... Stripecke, R. (2007). Lentiviral vectors with CMV or MHCII promoters administered in vivo: Immune reactivity versus persistence of expression. Molecular Therapy, 15(7), 1390-1399. https://doi.org/10.1038/sj.mt.6300180

Lentiviral vectors with CMV or MHCII promoters administered in vivo : Immune reactivity versus persistence of expression. / Kimura, Takahiro; Koya, Richard C.; Anselmi, Laura; Sternini, Catia; Wang, He Jing; Comin-Anduix, Begonya; Prins, Robert M.; Faure-Kumar, Emmanuelle; Rozengurt, Nora; Cui, Yan; Kasahara, Noriyuki; Stripecke, Renata.

In: Molecular Therapy, Vol. 15, No. 7, 01.07.2007, p. 1390-1399.

Research output: Contribution to journalArticle

Kimura, T, Koya, RC, Anselmi, L, Sternini, C, Wang, HJ, Comin-Anduix, B, Prins, RM, Faure-Kumar, E, Rozengurt, N, Cui, Y, Kasahara, N & Stripecke, R 2007, 'Lentiviral vectors with CMV or MHCII promoters administered in vivo: Immune reactivity versus persistence of expression', Molecular Therapy, vol. 15, no. 7, pp. 1390-1399. https://doi.org/10.1038/sj.mt.6300180
Kimura, Takahiro ; Koya, Richard C. ; Anselmi, Laura ; Sternini, Catia ; Wang, He Jing ; Comin-Anduix, Begonya ; Prins, Robert M. ; Faure-Kumar, Emmanuelle ; Rozengurt, Nora ; Cui, Yan ; Kasahara, Noriyuki ; Stripecke, Renata. / Lentiviral vectors with CMV or MHCII promoters administered in vivo : Immune reactivity versus persistence of expression. In: Molecular Therapy. 2007 ; Vol. 15, No. 7. pp. 1390-1399.
@article{9dd6f935c468405ba3f6b8016e887349,
title = "Lentiviral vectors with CMV or MHCII promoters administered in vivo: Immune reactivity versus persistence of expression",
abstract = "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.",
author = "Takahiro Kimura and Koya, {Richard C.} and Laura Anselmi and Catia Sternini and Wang, {He Jing} and Begonya Comin-Anduix and Prins, {Robert M.} and Emmanuelle Faure-Kumar and Nora Rozengurt and Yan Cui and Noriyuki Kasahara and Renata Stripecke",
year = "2007",
month = "7",
day = "1",
doi = "10.1038/sj.mt.6300180",
language = "English (US)",
volume = "15",
pages = "1390--1399",
journal = "Molecular Therapy",
issn = "1525-0016",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - Lentiviral vectors with CMV or MHCII promoters administered in vivo

T2 - Immune reactivity versus persistence of expression

AU - Kimura, Takahiro

AU - Koya, Richard C.

AU - Anselmi, Laura

AU - Sternini, Catia

AU - Wang, He Jing

AU - Comin-Anduix, Begonya

AU - Prins, Robert M.

AU - Faure-Kumar, Emmanuelle

AU - Rozengurt, Nora

AU - Cui, Yan

AU - Kasahara, Noriyuki

AU - Stripecke, Renata

PY - 2007/7/1

Y1 - 2007/7/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34250702619&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250702619&partnerID=8YFLogxK

U2 - 10.1038/sj.mt.6300180

DO - 10.1038/sj.mt.6300180

M3 - Article

VL - 15

SP - 1390

EP - 1399

JO - Molecular Therapy

JF - Molecular Therapy

SN - 1525-0016

IS - 7

ER -