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Biotechnol Appl Biochem ; 51(Pt 2): 97-105, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18215116

RESUMO

HCV (hepatitis C virus) is a worldwide health problem nowadays. No preventive vaccine is available against this pathogen, and therapeutic treatments currently in use have important drawbacks, including limited efficacy. In the present work a recombinant fowlpox virus, FPCoE1, expressing a truncated HCV core-E1 polyprotein, was generated. FPCoE1 virus generally failed to elicit a humoral immune response against HCV antigens in BALB/c mice. By contrast, mice inoculated with FPCoE1 elicited a positive interferon-gamma secretion response against HCV core in ex-vivo ELISPOT (enzyme-linked immunospot) assays. Remarkably, mice inoculated with FPCoE1 significantly controlled viraemia in a surrogate challenge model with vvRE, a recombinant vaccinia virus expressing HCV structural antigens. In fact, 40% of the mice had no detectable levels of vvRE in their ovaries. Administration of FPCoE1 in vervet monkeys [Chlorocebus (formerly Cercophitecus) aethiops sabaeus] induced lymphoproliferative response against HCV core and E1 proteins in 50% of immunized animals. Monkeys immunized with FPCoE1 had no detectable levels of vvRE in their blood, whereas monkeys inoculated with FP9, the negative control virus, had detectable levels of vvRE in blood up to 7 days after challenge. In conclusion, recombinant fowlpox virus FPCoE1 is able to induce an anti-HCV immune response in mice and monkeys. This ability could be rationally employed to develop effective strategies against HCV infection by using FPCoE1 in combination with other vaccine candidates or antiviral treatments.


Assuntos
Chlorocebus aethiops/imunologia , Vírus da Varíola das Aves Domésticas/genética , Hepatite C/imunologia , Imunização , Polimorfismo de Nucleotídeo Único/imunologia , Vaccinia virus/imunologia , Proteínas do Envelope Viral/imunologia , Animais , Chlorocebus aethiops/virologia , DNA Viral/genética , Ensaio de Imunoadsorção Enzimática , Feminino , Vírus da Varíola das Aves Domésticas/imunologia , Hepatite C/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único/genética , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas do Envelope Viral/administração & dosagem , Proteínas do Envelope Viral/genética
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