Epitope-focused immunogens targeting the hepatitis C virus glycoproteins induce broadly neutralizing antibodies

Nagarathinam K, Scheck A, Labuhn M, Ströh LJ, Herold E, Veselkova B, Tune S, Cramer JT, Rosset S, Vollers SS, Bankwitz D, Ballmaier M, Böning H, Roth E, Khera T, Ahsendorf-Abidi HP, Dittrich-Breiholz O, Obleser J, Nassal M, Jäck HM, Pietschmann T, Correia BE, Krey T (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Science Advances American Association for the Advancement of Science

Book Volume: 10

Article Number: eado2600

Journal Issue: 49

DOI: 10.1126/sciadv.ado2600

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.

Authors with CRIS profile

Hans-Martin Jäck Department of Molecular Immunology

Involved external institutions

Universitätsklinikum Freiburg DE Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) École Polytechnique Fédérale de Lausanne (EPFL) CH Switzerland (CH) Universität zu Lübeck DE Germany (DE)

How to cite

APA:

Nagarathinam, K., Scheck, A., Labuhn, M., Ströh, L.J., Herold, E., Veselkova, B.,... Krey, T. (2024). Epitope-focused immunogens targeting the hepatitis C virus glycoproteins induce broadly neutralizing antibodies. Science Advances, 10(49). https://doi.org/10.1126/sciadv.ado2600

MLA:

Nagarathinam, Kumar, et al. "Epitope-focused immunogens targeting the hepatitis C virus glycoproteins induce broadly neutralizing antibodies." Science Advances 10.49 (2024).

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