Plasma deconvolution identifies broadly neutralizing antibodies associated with hepatitis C virus clearance
Valerie J. Kinchen, … , James E. Crowe Jr, Justin R. Bailey
Valerie J. Kinchen, … , James E. Crowe Jr, Justin R. Bailey
Published August 13, 2019
Citation Information: J Clin Invest. 2019;129(11):4786-4796. https://doi.org/10.1172/JCI130720.
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Research Article Immunology Virology

Plasma deconvolution identifies broadly neutralizing antibodies associated with hepatitis C virus clearance

Abstract

A vaccine for hepatitis C virus (HCV) is urgently needed. Development of broadly neutralizing plasma antibodies during acute infection is associated with HCV clearance, but the viral epitopes of these plasma antibodies are unknown. Identifying these epitopes could define the specificity and function of neutralizing antibodies (NAbs) that should be induced by a vaccine. Here, we present the development and application of a high-throughput method that deconvolutes polyclonal anti-HCV NAbs in plasma, delineating the epitope specificities of anti-HCV NAbs in acute-infection plasma of 44 humans with subsequent clearance or persistence of HCV. Remarkably, we identified multiple broadly neutralizing antibody combinations that were associated with greater plasma neutralizing breadth and with HCV clearance. These studies have the potential to inform new strategies for vaccine development by identifying broadly neutralizing antibody combinations in plasma associated with the natural clearance of HCV, while also providing a high-throughput assay that could identify these responses after vaccination trials.

Authors

Valerie J. Kinchen, Guido Massaccesi, Andrew I. Flyak, Madeleine C. Mankowski, Michelle D. Colbert, William O. Osburn, Stuart C. Ray, Andrea L. Cox, James E. Crowe Jr, Justin R. Bailey

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Figure 4

Concordance between plasma deconvolution and mAbs isolated from B cells of the same subject.

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Concordance between plasma deconvolution and mAbs isolated from B cells ...
Deconvolution of NAb types in plasma of 2 subjects, C117 and C110, from whom reference mAbs were also isolated from B cells. Plasma neutralization profiles were averaged from 2 independent experiments, which were each performed in duplicate. Reference mAb profiles were averaged from 5 independent experiments, with each performed in duplicate. Wedge sizes are proportional to the plasma response attributed to each reference mAb. **Reference mAb detected in plasma was isolated from the B cells of the same subject. *Reference mAb detected in plasma and a mAb isolated from the B cells of this subject are of the same NAb type (i.e., they have positively correlated neutralization profiles and compete for E1/E2 binding). P values are for Pearson correlations of each plasma neutralization profile with a combined reference mAb neutralization profile comprising the indicated proportion of each reference mAb.