Epitope-focused immunogens targeting the hepatitis C virus glycoproteins induce broadly neutralizing antibodies
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
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Science advances. - 10, 49 (2024) , eado2600, ISSN: 2375-2548
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2025
- Urheber
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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
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10.1126/sciadv.ado2600
- URN
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urn:nbn:de:bsz:25-freidok-2613270
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:29 MESZ
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Beteiligte
- 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
Entstanden
- 2025
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