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

• Published in: Vaccine 2006-02, Vol.24 (9), p.1451-1461
• Main Authors: Klas, Sheri D., Lavine, Christy L., Whitt, Michael A., Miller, Mark A.
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - genetics; Adjuvants, Immunologic - pharmacology; Animals; Antibodies, Bacterial - blood; Applied microbiology; Bacterial Vaccines - immunology; Bacteriology; Biological and medical sciences; Cells, Cultured; Female; Fundamental and applied biological sciences. Psychology; Genetic Vectors; IL-12; Interferon-gamma - biosynthesis; Interleukin-12 - genetics; Interleukin-12 - pharmacology; Interleukin-2 - biosynthesis; Listeria monocytogenes; Listeria monocytogenes - immunology; Listeriosis - immunology; Listeriosis - pathology; Listeriosis - prevention & control; Liver - microbiology; Lymphocytes - immunology; Membrane Glycoproteins - genetics; Mice; Mice, Inbred C3H; Microbiology; Miscellaneous; Recombinant Fusion Proteins; Rodent; Spleen - microbiology; Vaccination; Vaccination - methods; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vesicular stomatitis Indiana virus - genetics; Vesicular stomatitis Indiana virus - immunology; Vesicular stomatitis Indiana virus - physiology; Vesicular stomatitis virus; Viral Envelope Proteins - genetics; Virus Replication
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2005.05.046

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 (VSVΔG-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 VSVΔG-IL12F elicits potent T cell- and B cell-mediated responses that confer protective listerial immunity.