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Journal of Virology, October 2001, p. 9068-9076, Vol. 75, No. 19
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.19.9068-9076.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Protection against Woodchuck Hepatitis Virus (WHV) Infection by Gene Gun Coimmunization with WHV Core and Interleukin-12

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,* and J. Prieto

Division of Hepatology and Gene Therapy, University Clinic and Medical School, University of Navarra, Pamplona, Spain

Received 29 May 2001/Accepted 29 June 2001

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.

* Corresponding author. Mailing address: Division of Hepatology and Gene Therapy, University of Navarra, C/Irunlarrea, no. 1, Pamplona C.P. 31008, Spain. Phone: 34 948 425600. Fax: 34 948 425649. E-mail: jruiz{at}unav.es.

Journal of Virology, October 2001, p. 9068-9076, Vol. 75, No. 19
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.19.9068-9076.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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