Protection against woodchuck hepatitis virus (WHV) infection by gene gun coimmunization with WHV core and interleukin-12.

Abstract

Woodchuck hepatitis virus (WHV) and hepatitis B virus (HBV) are closely similar with respect to genomic organization, host antiviral responses, and pathobiology of the infection. T-cell immunity against viral nucleocapsid (HBcAg or WHcAg) has been shown to play a critical role in viral clearance and protection against infection. Here we show that vaccination of healthy woodchucks by gene gun bombardment with a plasmid coding for WHcAg (pCw) stimulates proliferation of WHcAg-specific T cells but that these cells do not produce significant levels of gamma interferon (IFN-gamma) upon antigen stimulation. In addition, animals vaccinated with pCw alone were not protected against WHV inoculation. In order to induce a Th1 cytokine response, another group of woodchucks was immunized with pCw together with another plasmid coding for woodchuck interleukin-12 (IL-12). These animals exhibited WHcAg-specific T-cell proliferation with high IFN-gamma production and were protected against challenge with WHV, showing no viremia or low-level transient viremia after WHV inoculation. In conclusion, gene gun immunization with WHV core generates a non-Th1 type of response which does not protect against experimental infection. However, steering the immune response to a Th1 cytokine profile by IL-12 coadministration achieves protective immunity. These data demonstrate a crucial role of Th1 responses in the control of hepadnavirus replication and suggest new approaches to inducing protection against HBV infection.

• Authors: R García-Navarro, B Blanco-Urgoiti, P Berraondo, R Sánchez de la Rosa, A Vales, S Hervás-Stubbs, J J Lasarte, F Borrás, J Ruiz, J Prieto
• Journal: Journal of virology (J Virol) Vol. 75 Issue 19 Pg. 9068-76 (Oct 2001) ISSN: 0022-538X [Print] United States
• PMID: 11533170 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Viral Vaccines
• Interleukin-12

Topics

• Animals
• Biolistics
• Hepatitis B (immunology, prevention & control, virology)
• Hepatitis B Virus, Woodchuck (genetics, immunology)
• Interleukin-12 (genetics, immunology)
• Marmota
• Nucleocapsid (genetics, immunology)
• T-Lymphocytes (immunology)
• Viral Vaccines