Bankwitz, Dorothea, Bahai, Akash, Labuhn, Maurice, Doepke, Mandy, Ginkel, Corinne, Khera, Tanvi, Todt, Daniel ORCID: 0000-0002-3564-1014, Stroh, Luisa J., Dold, Leona, Klein, Florian, Klawonn, Frank, Krey, Thomas, Behrendt, Patrick, Cornberg, Markus ORCID: 0000-0002-9141-8001, McHardy, Alice C. and Pietschmann, Thomas (2021). Hepatitis C reference viruses highlight potent antibody responses and diverse viral functional interactions with neutralising antibodies. Gut, 70 (9). S. 1734 - 1746. LONDON: BMJ PUBLISHING GROUP. ISSN 1468-3288

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Abstract

Objective Neutralising antibodies are key effectors of infection-induced and vaccine-induced immunity. Quantification of antibodies' breadth and potency is critical for understanding the mechanisms of protection and for prioritisation of vaccines. Here, we used a unique collection of human specimens and HCV strains to develop HCV reference viruses for quantification of neutralising antibodies, and to investigate viral functional diversity. Design We profiled neutralisation potency of polyclonal immunoglobulins from 104 patients infected with HCV genotype (GT) 1-6 across 13 HCV strains representing five viral GTs. Using metric multidimensional scaling, we plotted HCV neutralisation onto neutralisation maps. We employed K-means clustering to guide virus clustering and selecting representative strains. Results Viruses differed greatly in neutralisation sensitivity, with J6 (GT2a) being most resistant and SA13 (GT5a) being most sensitive. They mapped to six distinct neutralisation clusters, in part composed of viruses from different GTs. There was no correlation between viral neutralisation and genetic distance, indicating functional neutralisation clustering differs from sequence-based clustering. Calibrating reference viruses representing these clusters against purified antibodies from 496 patients infected by GT1 to GT6 viruses readily identified individuals with extraordinary potent and broadly neutralising antibodies. It revealed comparable antibody cross-neutralisation and diversity between specimens from diverse viral GTs, confirming well-balanced reporting of HCV cross-neutralisation across highly diverse human samples. Conclusion Representative isolates from six neutralisation clusters broadly reconstruct the functional HCV neutralisation space. They enable high resolution profiling of HCV neutralisation and they may reflect viral functional and antigenic properties important to consider in HCV vaccine design.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Bankwitz, DorotheaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bahai, AkashUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Labuhn, MauriceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doepke, MandyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ginkel, CorinneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Khera, TanviUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Todt, DanielUNSPECIFIEDorcid.org/0000-0002-3564-1014UNSPECIFIED
Stroh, Luisa J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dold, LeonaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klawonn, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krey, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Behrendt, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cornberg, MarkusUNSPECIFIEDorcid.org/0000-0002-9141-8001UNSPECIFIED
McHardy, Alice C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pietschmann, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-598187
DOI: 10.1136/gutjnl-2020-321190
Journal or Publication Title: Gut
Volume: 70
Number: 9
Page Range: S. 1734 - 1746
Date: 2021
Publisher: BMJ PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1468-3288
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
INFECTION; RESISTANCE; CLEARANCE; REINFECTION; APPEARANCE; GENOTYPES; RECEPTOR; PROTECTMultiple languages
Gastroenterology & HepatologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59818

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