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dc.contributor.authorSalas, Jordan H
dc.contributor.authorUrbanowicz, Richard A
dc.contributor.authorGuest, Johnathan D
dc.contributor.authorFrumento, Nicole
dc.contributor.authorFigueroa, Alexis
dc.contributor.authorClark, Kaitlyn E
dc.contributor.authorKeck, Zhenyong
dc.contributor.authorCowton, Vanessa M
dc.contributor.authorCole, Sarah J
dc.contributor.authorPatel, Arvind H
dc.contributor.authorFuerst, Thomas R
dc.contributor.authorDrummer, Heidi E
dc.contributor.authorMajor, Marian
dc.contributor.authorTarr, Alexander W
dc.contributor.authorBall, Jonathan K
dc.contributor.authorLaw, Mansun
dc.contributor.authorPierce, Brian G
dc.contributor.authorFoung, Steven K H
dc.contributor.authorBailey, Justin R
dc.date.accessioned2022-02-10T20:22:58Z
dc.date.available2022-02-10T20:22:58Z
dc.date.issued2021-10-13
dc.identifier.urihttp://hdl.handle.net/10713/17949
dc.description.abstractBackground & aims: Development of a prophylactic hepatitis C virus (HCV) vaccine will require accurate and reproducible measurement of neutralizing breadth of vaccine-induced antibodies. Currently available HCV panels may not adequately represent the genetic and antigenic diversity of circulating HCV strains, and the lack of standardization of these panels makes it difficult to compare neutralization results obtained in different studies. Here, we describe the selection and validation of a genetically and antigenically diverse reference panel of 15 HCV pseudoparticles (HCVpps) for neutralization assays. Methods: We chose 75 envelope (E1E2) clones to maximize representation of natural polymorphisms observed in circulating HCV isolates, and 65 of these clones generated functional HCVpps. Neutralization sensitivity of these HCVpps varied widely. HCVpps clustered into 15 distinct groups based on patterns of relative sensitivity to 7 broadly neutralizing monoclonal antibodies. We used these data to select a final panel of 15 antigenically representative HCVpps. Results: Both the 65 and 15 HCVpp panels span 4 tiers of neutralization sensitivity, and neutralizing breadth measurements for 7 broadly neutralizing monoclonal antibodies were nearly equivalent using either panel. Differences in neutralization sensitivity between HCVpps were independent of genetic distances between E1E2 clones. Conclusions: Neutralizing breadth of HCV antibodies should be defined using viruses spanning multiple tiers of neutralization sensitivity rather than panels selected solely for genetic diversity. We propose that this multitier reference panel could be adopted as a standard for the measurement of neutralizing antibody potency and breadth, facilitating meaningful comparisons of neutralization results from vaccine studies in different laboratories.en_US
dc.description.urihttps://doi.org/10.1053/j.gastro.2021.10.005en_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofGastroenterologyen_US
dc.rightsCopyright © 2022 AGA Institute. All rights reserved.en_US
dc.subjectBroadly Neutralizing Antibodiesen_US
dc.subjectHepatitis C Virusen_US
dc.subjectNeutralizing Breadthen_US
dc.subjectVaccineen_US
dc.titleAn Antigenically Diverse, Representative Panel of Envelope Glycoproteins for Hepatitis C Virus Vaccine Development.en_US
dc.typeArticleen_US
dc.identifier.doi10.1053/j.gastro.2021.10.005
dc.identifier.pmid34655573
dc.source.journaltitleGastroenterology
dc.source.volume162
dc.source.issue2
dc.source.beginpage562
dc.source.endpage574
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited Kingdom
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States


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