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

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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

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Notes: Science advances. - 10, 49 (2024) , eado2600, ISSN: 2375-2548

Event: Veröffentlichung

(where): Freiburg

(who): Universität

(when): 2025

Creator: Nagarathinam, Kumar
Scheck, Andreas
Labuhn, Maurice
Ströh, Luisa Johanna
Herold, Elisabeth
Veselkova, Barbora
Tune, Sarah
Cramer, Johannes T.
Rosset, Stéphane
Vollers, Sabrina S.
Bankwitz, Dorothea
Ballmaier, Matthias
Böning, Heike
Roth, Edith
Khera, Tanvi
Ahsendorf-Abidi, Henrike P.
Dittrich-Breiholz, Oliver
Obleser, Jonas
Nassal, Michael
Jäck, Hans-Martin
Pietschmann, Thomas
Correia, Bruno E.
Krey, Thomas

DOI: 10.1126/sciadv.ado2600

URN: urn:nbn:de:bsz:25-freidok-2613270

Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 15.08.2025, 7:29 AM CEST

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Associated

Nagarathinam, Kumar
Scheck, Andreas
Labuhn, Maurice
Ströh, Luisa Johanna
Herold, Elisabeth
Veselkova, Barbora
Tune, Sarah
Cramer, Johannes T.
Rosset, Stéphane
Vollers, Sabrina S.
Bankwitz, Dorothea
Ballmaier, Matthias
Böning, Heike
Roth, Edith
Khera, Tanvi
Ahsendorf-Abidi, Henrike P.
Dittrich-Breiholz, Oliver
Obleser, Jonas
Nassal, Michael
Jäck, Hans-Martin
Pietschmann, Thomas
Correia, Bruno E.
Krey, Thomas
Universität

Time of origin

2025

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

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Other Objects (12)

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