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Cited by 12Hepatitis C virus researchMonoclonal and Polyclonal Antibodies Researchvaccines and immunoinformatics approaches

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

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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·2023·Nature Communications
DOI 10.1038/s41467-023-39690-0PMC PMC10328973

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Abstract

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.

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Metadata

Authors
Capella-Pujol, J., de Gast, M., Radić, L., Zon, I., Chumbe, A., Koekkoek, S., Olijhoek, W., Schinkel, J., van Gils, M. J., Sanders, R. W., & Sliepen, K.
Affiliations
  • Amsterdam University Medical Centers (NL)
  • Cornell University (US)
  • Amsterdam UMC Location University of Amsterdam (NL)
Corresponding author
  • Sanders, Rogier W.
  • Sliepen, Kwinten
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2023-07-07
Volume
14
Issue
1
Pages
4036-4036
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-023-39690-0
PMC
PMC10328973
OpenAlex
W4383499691
Cited by
12
References
3
Citations by year
2026: 3 · 2025: 5 · 2024: 3 · 2023: 1
FWCI
2.01
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Pure Amsterdam UMC (submittedVersion, cc-by)
Funders
  • Bill and Melinda Gates Foundation (OPP1156262)
  • Amsterdam University Medical Centers
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (91719372, 015.015.042)
  • National Institutes of Health (OPP1156262)
  • National Institute of Allergy and Infectious Diseases (OPP1156262)
  • Institute of Infection and Immunity
Topics
  • Health Sciences › Medicine › Hepatology › Hepatitis C virus research
  • Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
Keywords
hepatitis C virus, broadly neutralizing antibodies, B cell receptor activation, HCV vaccine design
MeSH terms
Broadly Neutralizing Antibodies, Hepatitis C, Humans, Recombinant Proteins, Viral Envelope Proteins, Hepacivirus, Antibodies, Neutralizing

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