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

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

Research output: Contribution to journalArticle

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. 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.

Original languageEnglish (US)
JournalThe Journal of clinical investigation
Volume130
DOIs
StatePublished - Aug 13 2019

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Neutralizing Antibodies
Hepacivirus
Epitopes
Hepatitis C Antibodies
Vaccines
Infection
Vaccination
Antibodies

Keywords

  • Adaptive immunity
  • Hepatitis
  • Immunoglobulins
  • Immunology
  • Virology

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Plasma deconvolution identifies broadly neutralizing antibodies associated with hepatitis C virus clearance. / Kinchen, Valerie J.; Massaccesi, Guido; Flyak, Andrew I.; Mankowski, Madeleine C.; Colbert, Michelle D.; Osburn, William; Ray, Stuart C.; Cox, Andrea L.; Crowe, James E.; Bailey, Justin R.

In: The Journal of clinical investigation, Vol. 130, 13.08.2019.

Research output: Contribution to journalArticle

Kinchen, VJ, Massaccesi, G, Flyak, AI, Mankowski, MC, Colbert, MD, Osburn, W, Ray, SC, Cox, AL, Crowe, JE & Bailey, JR 2019, 'Plasma deconvolution identifies broadly neutralizing antibodies associated with hepatitis C virus clearance', The Journal of clinical investigation, vol. 130. https://doi.org/10.1172/JCI130720
Kinchen, Valerie J. ; Massaccesi, Guido ; Flyak, Andrew I. ; Mankowski, Madeleine C. ; Colbert, Michelle D. ; Osburn, William ; Ray, Stuart C. ; Cox, Andrea L. ; Crowe, James E. ; Bailey, Justin R. / Plasma deconvolution identifies broadly neutralizing antibodies associated with hepatitis C virus clearance. In: The Journal of clinical investigation. 2019 ; Vol. 130.
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