Epitope-focused immunogens targeting the hepatitis C virus glycoproteins induce broadly neutralizing antibodies
Year: 2024
Type: article
Abstract: Hepatitis C virus (HCV) infection causes ~290,000 annual human deaths despite the highly effective antiviral treatment available. Several viral immune evasion mechanisms have hampered the development of an effective vaccine against HCV, among them the remarkable conformational flexibility within neutralization epitopes in the HCV antigens. Here, we report the design of epitope-focused immunogens displaying two distinct HCV cross-neutralization epitopes. We show that these immunogens induce a pronounced, broadly neutralizing antibody response in laboratory and transgenic human antibody mice. Monoclonal human antibodies isolated from immunized human antibody mice specifically recognized the grafted epitopes and neutralized four diverse HCV strains. Our results highlight a promising strategy for developing HCV immunogens and provide an encouraging paradigm for targeting structurally flexible epitopes to improve the induction of neutralizing antibodies.
Source: Science Advances
Authors: Kumar Nagarathinam, Andreas Scheck, Maurice Labuhn, Luisa J. Ströh, Elisabeth Herold, Barbora Veselkova, Sarah Tune, Johannes T. Cramer, Stéphane Rosset, Sabrina S. Vollers, Dorothea Bankwitz, Matthias Ballmaier, Heike Böning, Edith Roth, Tanvi Khera, Henrike P. Ahsendorf-Abidi, Oliver Dittrich-Breiholz, Jonas Obleser, Michael Nassal, Hans-Martin Jäck, Thomas Pietschmann, Bruno E. Correia, Thomas Krey
Institutions: University of Lübeck, SIB Swiss Institute of Bioinformatics, École Polytechnique Fédérale de Lausanne, Medizinische Hochschule Hannover, Helmholtz Centre for Infection Research, Center for Experimental and Clinical Infection Research, Friedrich-Alexander-Universität Erlangen-Nürnberg, University of Freiburg, University Medical Center Freiburg, German Center for Infection Research, Centre for Structural Systems Biology
Language: English
Topic: Hepatitis C virus research
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,500
Funder: Deutsche Forschungsgemeinschaft
OpenAlex ID: W4405103243