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Protection against woodchuck hepatitis virus (WHV) infection by gene gun coimmunization with WHV core and interleukin-12. 2001

R García-Navarro, and B Blanco-Urgoiti, and P Berraondo, and R Sánchez de la Rosa, and A Vales, and S Hervás-Stubbs, and J J Lasarte, and F Borrás, and J Ruiz, and J Prieto
Division of Hepatology and Gene Therapy, University Clinic and Medical School, University of Navarra, Pamplona, Spain.

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.

UI MeSH Term Description Entries
D008392 Marmota A genus of Sciuridae consisting of 14 species. They are shortlegged, burrowing rodents which hibernate in winter. Woodchucks,Marmots,Marmot,Marmotas,Woodchuck
D006509 Hepatitis B INFLAMMATION of the LIVER in humans caused by a member of the ORTHOHEPADNAVIRUS genus, HEPATITIS B VIRUS. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact. Hepatitis B Virus Infection
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D014765 Viral Vaccines Suspensions of attenuated or killed viruses administered for the prevention or treatment of infectious viral disease. Viral Vaccine,Vaccine, Viral,Vaccines, Viral
D017919 Hepatitis B Virus, Woodchuck An ORTHOHEPADNAVIRUS causing chronic liver disease and hepatocellular carcinoma in woodchucks. It closely resembles the human hepatitis B virus. Hepatitis Virus, Woodchuck,Woodchuck Hepatitis B Virus,Woodchuck Hepatitis Virus,Hepatitis Viruses, Woodchuck,Virus, Woodchuck Hepatitis,Viruses, Woodchuck Hepatitis,Woodchuck Hepatitis Viruses
D018664 Interleukin-12 A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-12 is a 70 kDa protein that is composed of covalently linked 40 kDa and 35 kDa subunits. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cells and plays a role in the stimulation of INTERFERON-GAMMA production by T-LYMPHOCYTES and NATURAL KILLER CELLS. Edodekin Alfa,IL-12,Natural Killer Cell Stimulatory Factor,Cytotoxic Lymphocyte Maturation Factor,IL 12,IL-12 p70,IL12,Interleukin 12,Interleukin-12 p70,Interleukin 12 p70
D019251 Nucleocapsid A protein-nucleic acid complex which forms part or all of a virion. It consists of a CAPSID plus enclosed nucleic acid. Depending on the virus, the nucleocapsid may correspond to a naked core or be surrounded by a membranous envelope. Nucleocapsids
D019470 Biolistics Techniques where DNA is delivered directly into organelles at high speed using projectiles coated with nucleic acid, shot from a helium-powered gun (gene gun). One of these techniques involves immunization by DNA VACCINES, which delivers DNA-coated gold beads to the epidermis. Gene-Gun Technique,Particle-Mediated Epidermal Delivery of DNA,Gene Gun DNA Immunization,Particle Mediated Epidermal Delivery of DNA,Biolistic,Gene Gun Technique,Gene-Gun Techniques

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