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 journalArticlepeer-review

57 Scopus citations

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

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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