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J Clin Invest. 2019 Aug 13;130. pii: 130720. doi: 10.1172/JCI130720.

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

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Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Department of Pediatrics, Vanderbilt University Medical Center.
Department of Pathology, Microbiology, and Immunology, and.
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Vanderbilt University, Nashville, Tennessee, USA.


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. Identification of these epitopes could define the specificity and function of neutralizing antibodies (NAbs) that should be induced by a vaccine. Here, we present 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 forty-four humans with subsequent clearance or persistence of HCV. Remarkably, we identified multiple broadly neutralizing antibody (bNAb) combinations that were associated with greater plasma neutralizing breadth and with HCV clearance. These studies have potential to inform new strategies for vaccine development by identifying bNAb combinations in plasma associated with natural clearance of HCV, while also providing a high-throughput assay that could identify these responses after vaccination trials.


Adaptive immunity; Hepatitis; Immunoglobulins; Immunology; Virology

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