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

Kinchen, Valerie J. and Massaccesi, Guido and Flyak, Andrew I. and Mankowski, Madeleine C. and Colbert, Michelle D. and Osburn, William O. and Ray, Stuart C. and Cox, Andrea L. and Crowe, James E., Jr. and Bailey, Justin R. (2019) Plasma deconvolution identifies broadly neutralizing antibodies associated with hepatitis C virus clearance. Journal of Clinical Investigation, 129 (11). pp. 4786-4796. ISSN 0021-9738. PMCID PMC6819096. https://resolver.caltech.edu/CaltechAUTHORS:20191121-075035817

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1172/jci130720DOIArticle
https://www.jci.org/articles/view/130720/sd/1PublisherSupplemental Data
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819096/PubMed CentralArticle
ORCID:
AuthorORCID
Kinchen, Valerie J.0000-0003-2317-9990
Massaccesi, Guido0000-0002-4528-0937
Flyak, Andrew I.0000-0002-8722-479X
Ray, Stuart C.0000-0002-1051-7260
Crowe, James E., Jr.0000-0002-0049-1079
Additional Information:© 2019 American Society for Clinical Investigation. Submitted: May 30, 2019; Accepted: August 1, 2019; Published: September 30, 2019. Author Contributions: JRB, SCR, and JEC conceived the study. VJK, MCM, MDC, and WOO performed experiments. JEC and AIF provided antibodies. VJK, GM, ALC, AIF, and JRB analyzed the data. VJK and JRB wrote the original draft. All authors reviewed and edited the manuscript. The authors would like to thank Alexander Gooden for technical support. This research was supported by NIH grants R01 AI127469 (to JRB) and U19 AI088791 (to JRB and ALC). AIF is a Cancer Research Institute Irvington Fellow supported by the Cancer Research Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Conflict of interest: AIF, JEC, and JRB are inventors of International Patent Application, Serial no. PCT/US2019/029315, pertaining to some of the antibodies presented in this article. JEC has served as a consultant for Takeda Vaccines, Sanofi Pasteur, Pfizer, and Novavax, is on the Scientific Advisory Boards of CompuVax, GigaGen, Meissa Vaccines, PaxVax, and is Founder of IDBiologics, Inc.
Funders:
Funding AgencyGrant Number
NIHR01 AI127469
NIHU19 AI088791
Cancer Research InstituteUNSPECIFIED
Issue or Number:11
PubMed Central ID:PMC6819096
Record Number:CaltechAUTHORS:20191121-075035817
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20191121-075035817
Official Citation:Plasma deconvolution identifies broadly neutralizing antibodies associated with hepatitis C virus clearance. Valerie J. Kinchen, … , James E. Crowe Jr, Justin R. Bailey. Published November 1, 2019; First published August 13, 2019. J. Clin. Invest. 2019; 129(11): 4786-4796. https://doi.org/10.1172/JCI130720.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:99972
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:21 Nov 2019 17:45
Last Modified:04 Dec 2019 18:13

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