Immunization with a lentivector that targets tumor antigen expression to dendritic cells induces potent CD8+ and CD4+ T-cell responses

Luciene Lopes, Marie Dewannieux, Uzi Gileadi, Ranbir Bailey, Yasuhiro Ikeda, Christopher Whittaker, Matthew P. Collin, Vincenzo Cerundolo, Mizuki Tomihari, Kiyoshi Ariizumi, Mary K. Collins

Research output: Contribution to journalArticle

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Abstract

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-Ab. 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.

Original languageEnglish (US)
Pages (from-to)86-95
Number of pages10
JournalJournal of Virology
Volume82
Issue number1
DOIs
StatePublished - Jan 2008

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Neoplasm Antigens
dendritic cells
Dendritic Cells
Immunization
immunization
T-lymphocytes
Transgenes
transgenes
antigens
T-Lymphocytes
neoplasms
mice
Green Fluorescent Proteins
green fluorescent protein
Vaccines
promoter regions
vaccines
Melanoma-Specific Antigens
HLA-A2 Antigen
antigen-presenting cells

ASJC Scopus subject areas

  • Immunology

Cite this

Immunization with a lentivector that targets tumor antigen expression to dendritic cells induces potent CD8+ and CD4+ T-cell responses. / Lopes, Luciene; Dewannieux, Marie; Gileadi, Uzi; Bailey, Ranbir; Ikeda, Yasuhiro; Whittaker, Christopher; Collin, Matthew P.; Cerundolo, Vincenzo; Tomihari, Mizuki; Ariizumi, Kiyoshi; Collins, Mary K.

In: Journal of Virology, Vol. 82, No. 1, 01.2008, p. 86-95.

Research output: Contribution to journalArticle

Lopes, L, Dewannieux, M, Gileadi, U, Bailey, R, Ikeda, Y, Whittaker, C, Collin, MP, Cerundolo, V, Tomihari, M, Ariizumi, K & Collins, MK 2008, 'Immunization with a lentivector that targets tumor antigen expression to dendritic cells induces potent CD8+ and CD4+ T-cell responses', Journal of Virology, vol. 82, no. 1, pp. 86-95. https://doi.org/10.1128/JVI.01289-07
Lopes, Luciene ; Dewannieux, Marie ; Gileadi, Uzi ; Bailey, Ranbir ; Ikeda, Yasuhiro ; Whittaker, Christopher ; Collin, Matthew P. ; Cerundolo, Vincenzo ; Tomihari, Mizuki ; Ariizumi, Kiyoshi ; Collins, Mary K. / Immunization with a lentivector that targets tumor antigen expression to dendritic cells induces potent CD8+ and CD4+ T-cell responses. In: Journal of Virology. 2008 ; Vol. 82, No. 1. pp. 86-95.
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