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Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Cooperativity in virus neutralization by human monoclonal antibodies to two adjacent regions located at the amino terminus of hepatitis C virus E2 glycoprotein

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. CO-HEP; Copenhagen Hepatitis C Program

    Projekt: Typer af projekter

  1. Replicons of a rodent hepatitis C model virus permit selection of highly permissive cells

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. IDENTIFICATION OF PIPERAZINYLBENZENESULFONAMIDES AS NEW INHIBITORS OF CLAUDIN-1 TRAFFICKING AND HEPATITIS C VIRUS ENTRY

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Development of a downstream process for the production of an inactivated whole hepatitis C virus vaccine

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Global and local envelope protein dynamics of hepatitis C virus determine broad antibody sensitivity

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. An alternate conformation of HCV E2 neutralizing face as an additional vaccine target

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer
A challenge for hepatitis C virus (HCV) vaccine development is defining conserved epitopes that induce protective antibodies against this highly diverse virus. An E2 segment located at amino acids (aa) 412-423 contains highly conserved neutralizing epitopes. While polyclonal antibodies to aa412-423 from HCV infected individuals confirmed broad neutralization, conflicting findings have been reported on polyclonal antibodies to an adjacent region, aa434-446, that may or may not interfere with neutralization by antibodies to aa412-423. To define the interplay between these antibodies, we isolated human monoclonal antibodies (HMAbs) to aa412-423, designated HC33-related HMAbs, and characterized their interaction with other HMAbs to aa434-446. A subset of the HC33 HMAbs neutralized genotype 1-6 HCVcc with varying activities. Although non-neutralizing HC33 HMAbs were isolated, they had lower binding affinity than neutralizing HC33 HMAbs. These antibodies could be converted to neutralizing antibodies by affinity maturation. Unidirectional competition for binding to E2 was observed between HC33 HMAbs and HMAbs to aa434-446. When HMAbs to aa434-446, which mediated neutralization, were combined with neutralizing HC33 HMAbs, biphasic patterns in neutralization were observed. A modest degree of antagonism was observed at lower concentrations and a modest degree of synergism was observed at higher concentrations. However, the overall effect was additive neutralization. A similar pattern was observed when these antibodies were combined to block E2 binding to the HCV co-receptor, CD81. These findings demonstrated that both of these E2 regions participate in epitopes mediating virus neutralization and those antibodies to aa412-423 and aa434-446 do not hinder their respective virus neutralizing activities.
OriginalsprogEngelsk
TidsskriftJournal of Virology
Vol/bind87
Udgave nummer1
Sider (fra-til)37-51
Antal sider15
ISSN0022-538X
DOI
StatusUdgivet - jan. 2013

ID: 36471855