Murine granulocyte-macrophage colony-stimulating factor expressed from a bicistronic simian immunodeficiency virus-based integrase-defective lentiviral vector does not enhance T-cell responses in mice

Zuleika Michelini, Donatella Negri, Mirella Biava, Silvia Baroncelli, Massimo Spada, Pasqualina Leone, Roberta Bona, Maria Blasi, Didier Nègre, Mary E. Klotman, Andrea Cara

Research output: Contribution to journalArticle

Abstract

As a prelude to immunization studies in nonhuman primates, we compared in mice the immunogenicity of a simian immunodeficiency virus (SIV)-based integrase (IN)-defective lentiviral vector (IDLV) encoding the model antigen-enhanced green fluorescence protein (eGFP) in the presence or absence of the murine granulocyte-macrophage colony-stimulating factor (mGM-CSF) expressed from an internal ribosomal entry site (IRES) sequence. BALB/c mice were immunized once intramuscularly with IDLV expressing eGFP alone or eGFP and mGM-CSF and immune responses were evaluated up to 90 days from the single intramuscular immunization. Results indicated that the mGM-CSF was unable to improve the magnitude and quality of the immune response against the eGFP transgene in the context of the SIV-based IDLV, as evaluated by enzyme-linked immunosorbent spot (ELISPOT) assays for interferon-γ (IFN-γ) and by intracellular cytokine staining for IFN-γ, interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNF-α). These findings suggest that for vaccination purposes, the presence of mGM-CSF expressed after the IRES in a SIV-based IDLV system does not favor the improvement of the immunological response against the transgene of interest. Further studies should investigate whether the selection of a different cytokine gene might improve the immune response against the transgene.

Original languageEnglish
Pages (from-to)512-520
Number of pages9
JournalViral Immunology
Volume27
Issue number10
DOIs
Publication statusPublished - Dec 1 2014

    Fingerprint

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Molecular Medicine
  • Medicine(all)

Cite this