Details

Autor(en) / Beteiligte

• Capella-Pujol, Joan
• de Gast, Marlon
• Radić, Laura
• Zon, Ian
• Chumbe, Ana
• Koekkoek, Sylvie
• Olijhoek, Wouter
• Schinkel, Janke
• van Gils, Marit J.
• Sanders, Rogier W.
• Sliepen, Kwinten

Titel

Signatures of VH1-69-derived hepatitis C virus neutralizing antibody precursors defined by binding to envelope glycoproteins

Ist Teil von

• Nature communications, 2023-07, Vol.14 (1), p.4036-4036, Article 4036

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2023

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• An effective preventive vaccine for hepatitis C virus (HCV) remains a major unmet need. Antigenic region 3 (AR3) on the E1E2 envelope glycoprotein complex overlaps with the CD81 receptor binding site and represents an important epitope for broadly neutralizing antibodies (bNAbs) and is therefore important for HCV vaccine design. Most AR3 bNAbs utilize the V H 1-69 gene and share structural features that define the AR3C-class of HCV bNAbs. In this work, we identify recombinant HCV glycoproteins based on a permuted E2E1 trimer design that bind to the inferred V H 1-69 germline precursors of AR3C-class bNAbs. When presented on nanoparticles, these recombinant E2E1 glycoproteins efficiently activate B cells expressing inferred germline AR3C-class bNAb precursors as B cell receptors. Furthermore, we identify critical signatures in three AR3C-class bNAbs that represent two subclasses of AR3C-class bNAbs that will allow refined protein design. These results provide a framework for germline-targeting vaccine design strategies against HCV. The burden of chronic hepatitis C virus infection is exacerbated by the lack of an effective vaccine. In this work, authors use a recombinant permuted (E2E1) HCV glycoprotein design to analyze the binding of different VH1-69-derived AR3-directed broadly neutralizing antibodies to the viral envelope glycoprotein.