8QP6

Crystal structure of Hepatitis C Virus E1 glycoprotein epitope 314-324 scaffold design 1W4K_08 in complex with neutralizing antibody F(ab) fragment IGH526

Summary for 8QP6

• Entry DOI: 10.2210/pdb8qp6/pdb
• Descriptor: 1W4K_08, F(ab) IGH526 (3 entities in total)
• Functional Keywords: scaffold protein, hcv immunogen, structural protein, complex
• Biological source: Pyrobaculum aerophilum; More
• Total number of polymer chains: 12
• Total formula weight: 435332.80

Authors

Nagarathinam, K.,Krey, T. (deposition date: 2023-09-30, release date: 2024-10-09, Last modification date: 2025-04-30)

Primary citation

Nagarathinam, K.,Scheck, A.,Labuhn, M.,Stroh, L.J.,Herold, E.,Veselkova, B.,Tune, S.,Cramer, J.T.,Rosset, S.,Vollers, S.S.,Bankwitz, D.,Ballmaier, M.,Boning, H.,Roth, E.,Khera, T.,Ahsendorf-Abidi, H.P.,Dittrich-Breiholz, O.,Obleser, J.,Nassal, M.,Jack, H.M.,Pietschmann, T.,Correia, B.E.,Krey, T.
Epitope-focused immunogens targeting the hepatitis C virus glycoproteins induce broadly neutralizing antibodies.
Sci Adv, 10:eado2600-eado2600, 2024

PubMed 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.

PubMed: 39642219
DOI: 10.1126/sciadv.ado2600

Experimental method

X-RAY DIFFRACTION (2.59 Å)