Human monoclonal antibodies binding to epitopes common to type 1 and 2 HCV
are provided, as well as conformationally conserved HCV E2 2a and 2b
proteins. Compositions comprising the antibodies find use in diagnosis and
therapy. The antibodies recognize conformational epitopes that are
conserved across multiple genotypes of HCV. Thus the antibodies have the
potential to be useful in the prevention and treatment of the majority of
HCV infections. A subset of the antibodies (CBH-2, CBH-5, CBH-7, CBH-8C,
CBH-8E, and CBH-11) have the ability to prevent the binding of HCV E2
proteins of multiple genotypes to human CD81, a possible co-receptor for
HCV infection. A subset of the antibodies (CBH-2 and CBH-5) have been
shown to inhibit the binding of HCV virions (as opposed to purified E2
protein) to human CD81. A further subset of the antibodies (CBH-4D, CBH4B,
CBH-8C, and CBH-9) have been shown to prevent HCV envelope mediated fusion
using an HCV psuedotype system.
Os antibodies monoclonal humanos que ligam aos epitopes comuns a HCV do tipo 1 e 2 são fornecidos, assim como HCV conformationally conservado as proteínas 2a e 2b de E2. As composições que compreendem os antibodies encontram o uso no diagnóstico e na terapia. Os antibodies reconhecem os epitopes do conformational que são conservados através dos genotypes múltiplos de HCV. Assim os antibodies têm o potencial ser úteis na prevenção e no tratamento da maioria de infecções de HCV. Um subconjunto dos antibodies (CBH-2, CBH-5, CBH-7, CBH-8C, CBH-8E, e CBH-11) tem a abilidade de impedir o emperramento de proteínas de HCV E2 de genotypes múltiplos a CD81 humano, um co-co-receptor possível para a infecção de HCV. Um subconjunto dos antibodies (CBH-2 e CBH-5) foi mostrado para inibir o emperramento de virions de HCV (ao contrário da proteína E2 purified) a CD81 humano. Um subconjunto mais adicional dos antibodies (CBH-4D, CBH4B, CBH-8C, e CBH-9) foi mostrado para impedir a fusão mediada envelope de HCV usando um sistema do psuedotype de HCV.
