Protection against woodchuck hepatitis virus (WHV) infection by gene gun coimmunization with WHV core and interleukin-12.
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.
García-Navarro
R
R
Division of Hepatology and Gene Therapy, University Clinic and Medical School, University of Navarra, Pamplona, Spain.
Blanco-Urgoiti
B
B
Berraondo
P
P
Sánchez de la Rosa
R
R
Vales
A
A
Hervás-Stubbs
S
S
Lasarte
J J
JJ
Borrás
F
F
Ruiz
J
J
Prieto
J
J
D000818:Animals; D019470:Biolistics; D006509:Hepatitis B / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D017919:Hepatitis B Virus, Woodchuck / Q000235:genetics / Q000276:immunology*; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D008392:Marmota; D019251:Nucleocapsid / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014765:Viral Vaccines
D014765:Viral Vaccines; D018664:Interleukin-12