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Hepatitis C reference viruses highlight potent antibody responses and diverse viral functional interactions with neutralising antibodies

Authors :
Daniel Todt
Alice C. McHardy
Frank Klawonn
Dorothea Bankwitz
Mandy Doepke
Thomas Pietschmann
Markus Cornberg
Tanvi Khera
Patrick Behrendt
Akash Bahai
Florian Klein
Leona Dold
Thomas Krey
Corinne Ginkel
Luisa J Ströh
Maurice Labuhn
TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
Source :
Gut, England
Publication Year :
2020
Publisher :
BMJ, 2020.

Abstract

ObjectiveNeutralising 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.DesignWe 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.ResultsViruses 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.ConclusionRepresentative 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.

Details

ISSN :
14683288 and 00175749
Volume :
70
Database :
OpenAIRE
Journal :
Gut
Accession number :
edsair.doi.dedup.....b00fb6348d405a36d92e514c3936c636
Full Text :
https://doi.org/10.1136/gutjnl-2020-321190