Coexpression of GM-CSF and antigen in DNA prime-adenoviral vector boost immunization enhances polyfunctional CD8+ T cell responses, whereas expression of GM-CSF antigen fusion protein induces autoimmunity.

BMC Immunology
M TenbuschK Uberla

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has shown promising results as a cytokine adjuvant for antiviral vaccines and in various models of tumor gene therapy. To explore whether the targeting of antigens to GM-CSF receptors on antigen-presenting cells enhances antigen-specific CD8 T-cell responses, fusion proteins of GM-CSF and ovalbumin (OVA) were expressed by DNA and adenoviral vector vaccines. In addition, bicistronic vectors allowing independent expression of the antigen and the cytokine were tested in parallel. In vitro, the GM-CSF ovalbumin fusion protein (GM-OVA) led to the better stimulation of OVA-specific CD8+ T cells by antigen-presenting cells than OVA and GM-CSF given as two separate proteins. However, prime-boost immunizations of mice with DNA and adenoviral vector vaccines encoding GM-OVA suppressed CD8+ T-cell responses to OVA. OVA-specific IgG2a antibody levels were also reduced, while the IgG1 antibody response was enhanced. Suppression of CD8+ T cell responses by GM-OVA vaccines was associated with the induction of neutralizing antibodies to GM-CSF. In contrast, the coexpression of GM-CSF and antigens in DNA prime adenoviral boost immunizations led to a striking expansion of polyfunctional O...Continue Reading

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Citations

Jan 22, 2013·Applied Biochemistry and Biotechnology·Nidhi Chaubey, Siddhartha Sankar Ghosh
Sep 18, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Miguel-Angel PeralesJedd D Wolchok
Jul 4, 2016·Cancer Immunology, Immunotherapy : CII·Christoph HoellerChristian U Blank

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
transfection
transfections
transgenic
FACS
ELISA
dot blots
flow cytometry
glycosylation
PCR
FCS

Software Mentioned

AdEasy
Prism
GraphPad

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