Weber, Timm ORCID: 0000-0003-2079-842X, Potthoff, Julian, Bizu, Sven ORCID: 0000-0003-4839-2472, Labuhn, Maurice, Dold, Leona, Schoofs, Till, Horning, Marcel ORCID: 0000-0003-1468-4645, Ercanoglu, Meryem S., Kreer, Christoph ORCID: 0000-0002-9140-9850, Gieselmann, Lutz ORCID: 0000-0003-3699-3318, Vanshylla, Kanika ORCID: 0000-0003-4552-9170, Langhans, Bettina, Janicki, Hanna, Stroeh, Luisa J., Knops, Elena, Nierhoff, Dirk, Spengler, Ulrich, Kaiser, Rolf, Bjorkman, Pamela J., Krey, Thomas, Bankwitz, Dorothea, Pfeifer, Nico ORCID: 0000-0002-4647-8566, Pietschmann, Thomas, Flyak, Andrew, I and Klein, Florian ORCID: 0000-0003-1376-1792 (2022). Analysis of antibodies from HCV elite neutralizers identifies genetic determinants of broad neutralization. Immunity, 55 (2). S. 341 - 363. CAMBRIDGE: CELL PRESS. ISSN 1097-4180

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Abstract

The high genetic diversity of hepatitis C virus (HCV) complicates effective vaccine development. We screened a cohort of 435 HCV-infected individuals and found that 2%-5% demonstrated outstanding HCV-neutralizing activity. From four of these patients, we isolated 310 HCV antibodies, including neutralizing antibodies with exceptional breadth and potency. High neutralizing activity was enabled by the use of the VH1-69 heavy chain gene segment, somatic mutations within CDRH1, and CDRH2 hydrophobicity. Structural and mutational analyses revealed an important role for mutations replacing the serines at positions 30 and 31, as well as the presence of neutral and hydrophobic residues at the tip of the CDRH3. Based on these characteristics, we computationally created a de novo antibody with a fully synthetic VH1-69 heavy chain that efficiently neutralized multiple HCV genotypes. Our findings provide a deep understanding of the generation of broadly HCV-neutralizing antibodies that can guide the design of effective vaccine candidates.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Weber, TimmUNSPECIFIEDorcid.org/0000-0003-2079-842XUNSPECIFIED
Potthoff, JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bizu, SvenUNSPECIFIEDorcid.org/0000-0003-4839-2472UNSPECIFIED
Labuhn, MauriceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dold, LeonaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schoofs, TillUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Horning, MarcelUNSPECIFIEDorcid.org/0000-0003-1468-4645UNSPECIFIED
Ercanoglu, Meryem S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kreer, ChristophUNSPECIFIEDorcid.org/0000-0002-9140-9850UNSPECIFIED
Gieselmann, LutzUNSPECIFIEDorcid.org/0000-0003-3699-3318UNSPECIFIED
Vanshylla, KanikaUNSPECIFIEDorcid.org/0000-0003-4552-9170UNSPECIFIED
Langhans, BettinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janicki, HannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stroeh, Luisa J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knops, ElenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nierhoff, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spengler, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaiser, RolfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bjorkman, Pamela J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krey, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bankwitz, DorotheaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfeifer, NicoUNSPECIFIEDorcid.org/0000-0002-4647-8566UNSPECIFIED
Pietschmann, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Flyak, Andrew, IUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, FlorianUNSPECIFIEDorcid.org/0000-0003-1376-1792UNSPECIFIED
URN: urn:nbn:de:hbz:38-692273
DOI: 10.1016/j.immuni.2021.12.003
Journal or Publication Title: Immunity
Volume: 55
Number: 2
Page Range: S. 341 - 363
Date: 2022
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4180
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HEPATITIS-C VIRUS; MONOCLONAL-ANTIBODIES; B-CELLS; INFECTION; HIV-1; IMMUNOGLOBULIN; RECEPTOR; CHIMPANZEES; CLEARANCE; FUSIONMultiple languages
ImmunologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69227

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