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...

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Detalles Bibliográficos
Autores: Garcia-Navarro, R. (Raquel)|||/items/9c09be64-f0be-4416-9a09-f79c70d15934, Blanco-Urgoiti, B. (Begoña)|||/items/2728c716-9ca1-401e-9f5a-20fb7915c856, Berraondo-López, P. (Pedro)|||/items/b1f8ccc3-8e08-4ece-967c-64ccfc0e5b91, Sanchez-de-la-Rosa, R. (R.)|||/items/6e2c2d07-6df2-4e3c-973e-5b6205f5a759, Vales, A. (África)|||/items/f3b4e7dd-a2f9-4e77-9562-32b512a3772a, Hervas-Stubbs, S. (Sandra)|||/items/8f56cb52-4465-4428-8acf-e50439c6be8f, Lasarte-Sagastibelza, J.J. (Juan José)|||/items/e366ad83-3db4-41ec-a9da-ed9159ba5c0c, Borras-Cuesta, F. (Francisco)|||/items/9f3719bd-4cf6-4e5b-b672-39179b54e8cc, Ruiz, J. (Juan)|||/items/e71ee758-aef7-4ed6-b282-e483e9d9ba8e, Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71
Tipo de recurso: artículo
Fecha de publicación:2001
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/20619
Acceso en línea:https://hdl.handle.net/10171/20619
Access Level:acceso abierto
Palabra clave:Hepatitis B/immunology
Hepatitis B/prevention & control
Hepatitis B Virus, Woodchuck/immunology
Interleukin-12/immunology
Descripción
Sumario: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.

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