ArticleImmunity2022
Analysis of antibodies from HCV elite neutralizers identifies genetic determinants of broad neutralization.
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Article in Immunity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30citing papers in PubMed
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30 citing papers in PubMed, 51 citations in OpenAlex.
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- mAbClust with AlphaFold 3 avoids hallucinations to define a quaternary broadly neutralizing HCV epitope.bioRxiv : the preprint server for biology · 2026Article
- Antibody responses to a highly conserved peptide in HCV E2 protein correlate with chronicity or spontaneous clearance of HCV infection.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Use of Human Liver Chimeric Mice to Study Hepatitis C Virus Antibody Escape: Implications for Vaccine Development.Cellular and molecular gastroenterology and hepatology · 2026Article
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- The 14th Canadian Symposium on Hepatitis C Virus: From research breakthroughs to equitable health care for priority populations.Canadian liver journal · 2025Article
- Cryo-EM structures of HCV E2 glycoprotein bound to neutralizing and non-neutralizing antibodies determined using bivalent Fabs as fiducial markers.Communications biology · 2025Article
- Structural basis for hepatitis E virus neutralization by potent human antibodies.Science advances · 2025Article
- Bispecific antibodies against the hepatitis C virus E1E2 envelope glycoprotein.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Discovery of Antibodies Against Endemic Coronaviruses with NGS-Based Human Fab Phage Display Platform.Antibodies (Basel, Switzerland) · 2025Article
- Selection and characterization of a broadly neutralizing class of HCV anti-E2 VH1-69 antibodies.PLoS pathogens · 2025Article
- Broadly neutralizing antibodies isolated from HEV convalescents confer protective effects in human liver-chimeric mice.Nature communications · 2025Article
- A single residue switch mediates the broad neutralization of Rotaviruses.Nature communications · 2025Article
- Epitope-focused immunogens targeting the hepatitis C virus glycoproteins induce broadly neutralizing antibodies.Science advances · 2024Article
- B cells expressing mutated IGHV1-69-encoded antigen receptors related to virus neutralization show lymphoma-like transcriptomes in patients with chronic HCV infection.Hepatology communications · 2024Article
- Determination of the frequency of individuals with broadly cross-reactive neutralizing antibodies against PRRSV in the sow population under field conditions.Porcine health management · 2024Article
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Authors and funding
25 authors at 7 institutions in 2 countries.
Timm WeberLaboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
Julian PotthoffLaboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
Sven BizuMethods in Medical Informatics, Department of Computer Science, University of Tübingen, 72076 Tübingen, Germany.
Maurice LabuhnTwincore, Centre for Experimental and Clinical Infection Research, Institute of Experimental Virology, 30625 Hannover, Germany.
Leona DoldLaboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; Department of Internal Medicine I, University Hospital of Bonn, 53127 Bonn, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 50931 Cologne, Germany.
Till SchoofsLaboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
Marcel HorningLaboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
Meryem S ErcanogluLaboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
Christoph KreerLaboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
Lutz GieselmannLaboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 50931 Cologne, Germany.
Kanika VanshyllaLaboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
Bettina LanghansDepartment of Internal Medicine I, University Hospital of Bonn, 53127 Bonn, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 50931 Cologne, Germany.
Hanna JanickiLaboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
Luisa J StröhInstitute of Virology, Hannover Medical School, 30625 Hannover, Germany.
Elena KnopsInstitute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
Dirk NierhoffDepartment of Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, 50931 Cologne, Germany.
Ulrich SpenglerDepartment of Internal Medicine I, University Hospital of Bonn, 53127 Bonn, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 50931 Cologne, Germany.
Rolf KaiserGerman Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 50931 Cologne, Germany; Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
Pamela J BjorkmanDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Thomas KreyInstitute of Virology, Hannover Medical School, 30625 Hannover, Germany; Center of Structural and Cell Biology in Medicine, Institute of Biochemistry, University of Lübeck, 23562 Luebeck, Germany; Centre for Structural Systems Biology (CSSB), 22607 Hamburg, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg-Luebeck-Borstel-Riems, 23562 Luebeck, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, 30625 Hannover, Germany.
Dorothea BankwitzTwincore, Centre for Experimental and Clinical Infection Research, Institute of Experimental Virology, 30625 Hannover, Germany.
Nico PfeiferMethods in Medical Informatics, Department of Computer Science, University of Tübingen, 72076 Tübingen, Germany.
Thomas PietschmannTwincore, Centre for Experimental and Clinical Infection Research, Institute of Experimental Virology, 30625 Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, 30625 Hannover, Germany; German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, 30625 Hannover, Germany.
Andrew I FlyakDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Florian KleinLaboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 50931 Cologne, Germany; Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University of Cologne, 50931 Cologne, Germany. Electronic address: florian.klein@uk-koeln.de.
University of Cologne · DEMedizinische Hochschule Hannover · DECalifornia Institute of Technology · USCenter for Experimental and Clinical Infection Research · DEUniversity Hospital Bonn · DEUniversity of Tübingen · DEUniversity Hospital Cologne · DE
Funding
X-ray Absorption Spectroscopy (XAS) pp.711-759P41GM103393 · NIGMS · STANFORD UNIVERSITY · PI HODGSON, KEITH O · 2012 to 2019
$30.6MMolecular and structural characterization of broadly neutralizing anti-HCV antibodiesR01AI127469 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Justin Richard Bailey · 2017 to 2026
$6.8MImmunization strategies to elicit broadly neutralizing antibodies against HCVK99AI153465 · NIAID · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI FLYAK, ANDREW I · 2020 to 2021
$259kNIAID NIH HHS K99 AI153465NIAID NIH HHS R01 AI127469NIGMS NIH HHS P41 GM103393
Abstract
The high genetic diversity of hepatitis C virus (HCV) complicates effective vaccine development. We screened a cohort of 435 HCV-infected individuals and found that 2%-5% demonstrated outstanding HCV-neutralizing activity. From four of these patients, we isolated 310 HCV antibodies, including neutralizing antibodies with exceptional breadth and potency. High neutralizing activity was enabled by the use of the VH1-69 heavy-chain gene segment, somatic mutations within CDRH1, and CDRH2 hydrophobicity. Structural and mutational analyses revealed an important role for mutations replacing the serines at positions 30 and 31, as well as the presence of neutral and hydrophobic residues at the tip of the CDRH3. Based on these characteristics, we computationally created a de novo antibody with a fully synthetic VH1-69 heavy chain that efficiently neutralized multiple HCV genotypes. Our findings provide a deep understanding of the generation of broadly HCV-neutralizing antibodies that can guide the design of effective vaccine candidates.
Indexed as
B-LymphocytesBroadly Neutralizing AntibodiesComplementarity Determining RegionsEpitopesFemaleGenotypeHepacivirusHepatitis CHepatitis C AntibodiesHumansImmunoglobulin Heavy ChainsMaleMiddle AgedMutationViral Envelope ProteinsBroadly Neutralizing AntibodiesComplementarity Determining RegionsEpitopesglycoprotein E2, Hepatitis C virusHepatitis C AntibodiesImmunoglobulin Heavy ChainsViral Envelope Proteinselite neutralizerHCVhepatitis C virusmachine learningmonoclonal antibodyneutralizing antibodysingle B cell analysissomatic mutationV(H)1-69
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