ArticleNature communications2026
Structure-based design of stable recombinant hepatitis C virus E1E2 heterodimers.
Joan Capella-Pujol, Fabian Mulder, Fabien Cannac, Stan Peters, Maddy L Newby, Meliawati Poniman, Ian Zon, Wouter Olijhoek, Tim Beaumont, Max Crispin and 4 more
Abstract read
In one paragraphArticle in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 · Who and what moneyAuthors and funding
14 authors.
Joan Capella-Pujol *Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-7375-7958 Fabian Mulder *Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.ORCID http://orcid.org/0009-0009-1298-0740 Fabien CannacDepartment of Integrative Structural Biology and Computational Biology, The Scripps Research Institute, La Jolla, USA.
Stan PetersDepartment of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.ORCID http://orcid.org/0009-0007-7488-8478 Maddy L NewbySchool of Biological Sciences, University of Southampton, Southampton, UK.
Meliawati PonimanDepartment of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Ian ZonDepartment of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Wouter OlijhoekDepartment of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Tim BeaumontDepartment of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Janke SchinkelDepartment of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Rogier W SandersDepartment of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-2324-8573 Kwinten SliepenDepartment of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. k.h.sliepen@amsterdamumc.nl.ORCID http://orcid.org/0000-0003-1414-0648 Funding
Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation) OPP1153692Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation) OPP1156262Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research) 91719372
6 · The paper itselfAbstract
Hepatitis C virus (HCV) affects 47 million people and causes 239,000 deaths annually, yet no vaccine is on the horizon. Generating a stable native-like mimic of the envelope complex E1E2, the only target for known neutralizing antibodies, is an important aim for HCV vaccine development. Starting from a recombinant E1E2 design that utilizes a leucine zipper for proper folding, we used an iterative structure-based design approach to engineer antigens with at least 100-fold stronger binding to conformational antibodies and increased thermal stability. These new E1E2 designs facilitate production of native-like E1E2 antigens based on strains from different HCV genotypes and enable the generation of a recombinant E1E2 antigen design that lacks the immunogenic leucine zipper. A cryo-EM structure of one of the stabilized E1E2 antigens in complex with neutralizing antibody AT1211 provides atomic-level insights into an atypical epitope on the E2 subunit. Finally, immunogenicity studies in rabbits with adjuvanted E1E2 proteins show that immunogen stabilization alone does do not enhance serum neutralization breadth, but that removing the leucine zipper does increase homologous serum neutralization.
Indexed as
HepacivirusViral Envelope ProteinsViral Hepatitis VaccinesAnimalsAntibodies, NeutralizingCryoelectron MicroscopyEpitopesHepatitis CHepatitis C AntibodiesHumansLeucine ZippersProtein EngineeringProtein MultimerizationProtein Subunit VaccinesRabbitsRecombinant ProteinsAntibodies, NeutralizingE1 protein, Hepatitis C virusEpitopesglycoprotein E2, Hepatitis C virusHepatitis C AntibodiesProtein Subunit VaccinesRecombinant ProteinsViral Envelope ProteinsViral Hepatitis Vaccines
Identifiers
PMID42642377
PMCPMC13507286
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