Adjuvanticity of an IL-12 fusion protein expressed by recombinant deltaG-vesicular stomatitis virus.

The remarkable immunomodulatory and adjuvant properties of rIL-12 have been well described. Many early studies documenting the adjuvanticity of IL-12 were performed using the murine model of Listeria monocytogenes infection. In this report, we describe the construction of an attenuated recombinant vesicular stomatitis virus (VSV-deltaG) that encodes a single-chain IL-12 fusion protein (IL-12F), and the use of this virus as an expression vector to produce large quantities of IL-12F. VSV-expressed IL-12F (vIL-12F) was then co-administered to mice along with a poorly immunogenic listerial antigen preparation as a vaccine regimen and the resulting immune responses were monitored. The vIL-12F was found to have adjuvant properties similar to those observed for rIL-12. Co-administration of vIL-12F and listerial antigen elicited powerful cell-mediated immune responses that conferred long-lived protective listerial immunity. These studies demonstrated that VSVdeltaG-IL12F-infected cells secrete bioactive single-chain IL-12, and laid the foundation for studies using VSVdeltaG-IL12F as a vector for delivery of IL-12F in vivo.
AuthorsSheri D Klas, Clinton S Robison, Michael A Whitt, Mark A Miller
JournalCellular immunology (Cell Immunol) 2002 Jul-Aug Vol. 218 Issue 1-2 Pg. 59-73 ISSN: 0008-8749 [Print] United States
PMID12470614 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Adjuvants, Immunologic
  • Antigens, Bacterial
  • Bacterial Vaccines
  • G protein, vesicular stomatitis virus
  • Membrane Glycoproteins
  • Recombinant Fusion Proteins
  • Viral Envelope Proteins
  • Interleukin-12
  • Adjuvants, Immunologic (pharmacology)
  • Animals
  • Antigens, Bacterial (immunology)
  • Ascitic Fluid (cytology)
  • Bacterial Vaccines (immunology)
  • Cell Line
  • Cricetinae
  • Defective Viruses (genetics)
  • Female
  • Gene Deletion
  • Genetic Vectors (genetics)
  • Immunity, Cellular
  • Immunization
  • Interleukin-12 (pharmacology)
  • Listeria monocytogenes (immunology, isolation & purification)
  • Listeriosis (immunology, microbiology, prevention & control)
  • Liver (microbiology)
  • Membrane Glycoproteins (deficiency, genetics)
  • Mice
  • Mice, Inbred C3H
  • Recombinant Fusion Proteins (pharmacology)
  • Spleen (microbiology)
  • Vesicular stomatitis Indiana virus (genetics)
  • Viral Envelope Proteins (deficiency, genetics)

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