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.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Michelini, Z; Negri, D; Biava, M; Baroncelli, S; Spada, M; Leone, P; Bona, R; Blasi, M; Nègre, D; Klotman, ME; Cara, A

Published Date

  • December 2014

Published In

Volume / Issue

  • 27 / 10

Start / End Page

  • 512 - 520

PubMed ID

  • 25343523

Electronic International Standard Serial Number (EISSN)

  • 1557-8976

International Standard Serial Number (ISSN)

  • 0882-8245

Digital Object Identifier (DOI)

  • 10.1089/vim.2014.0062

Language

  • eng