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.
Klas
Sheri D
SD
Department of Molecular Sciences, University of Tennessee Health Science Center, 858 Madison Avenue, Memphis, TN 38163, USA.
Robison
Clinton S
CS
Whitt
Michael A
MA
Miller
Mark A
MA
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001202:Ascitic Fluid / Q000166:cytology; D001428:Bacterial Vaccines / Q000276:immunology*; D002460:Cell Line; D006224:Cricetinae; D003673:Defective Viruses / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005822:Genetic Vectors / Q000235:genetics*; D007111:Immunity, Cellular; D007114:Immunization; D018664:Interleukin-12 / Q000494:pharmacology*; D008089:Listeria monocytogenes / Q000276:immunology* / Q000302:isolation & purification; D008088:Listeriosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D008099:Liver / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013154:Spleen / Q000382:microbiology; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics*; D014759:Viral Envelope Proteins / Q000172:deficiency / Q000235:genetics
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D018664:Interleukin-12