IL-12-assisted immunization against Listeria monocytogenes using replication-restricted VSV-based vectors

Vaccine. 2006 Feb 27;24(9):1451-61. doi: 10.1016/j.vaccine.2005.05.046. Epub 2005 Sep 23.

Abstract

Co-administration of IL-12 with vaccine immunogens has proven to be an effective strategy for eliciting potent Th1-biased immunity. Unfortunately, the use of IL-12 as a vaccine component has been limited because it is unstable at ambient temperatures, expensive to produce, and toxic when administered at excessive dosages. Using reverse genetics, we created a recombinant replication-restricted vesicular stomatitis virus that expresses large quantities of an IL-12 fusion protein (VSVDeltaG-IL12F), but can only establish a single round of infection because the genome does not encode the viral glycoprotein (G protein) that is required for viral entry into host cells. Here, we report that immunization of mice with a poorly immunogenic listerial antigen preparation (LMAg) in combination with VSVDeltaG-IL12F elicits potent T cell- and B cell-mediated responses that confer protective listerial immunity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / genetics
  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antibodies, Bacterial / blood
  • Bacterial Vaccines / immunology*
  • Cells, Cultured
  • Female
  • Genetic Vectors
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / genetics
  • Interleukin-12 / pharmacology*
  • Interleukin-2 / biosynthesis
  • Listeria monocytogenes / immunology*
  • Listeriosis / immunology
  • Listeriosis / pathology
  • Listeriosis / prevention & control*
  • Liver / microbiology
  • Lymphocytes / immunology
  • Membrane Glycoproteins / genetics
  • Mice
  • Mice, Inbred C3H
  • Recombinant Fusion Proteins
  • Spleen / microbiology
  • Vaccination / methods*
  • Vesicular stomatitis Indiana virus / genetics*
  • Vesicular stomatitis Indiana virus / immunology
  • Vesicular stomatitis Indiana virus / physiology
  • Viral Envelope Proteins / genetics
  • Virus Replication

Substances

  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Bacterial Vaccines
  • G protein, vesicular stomatitis virus
  • Interleukin-2
  • Membrane Glycoproteins
  • Recombinant Fusion Proteins
  • Viral Envelope Proteins
  • Interleukin-12
  • Interferon-gamma