Evidence map›Paper›PMID 34655573›Full record

ArticleGastroenterology2022

An Antigenically Diverse, Representative Panel of Envelope Glycoproteins for Hepatitis C Virus Vaccine Development.

Jordan H Salas, Richard A Urbanowicz, Johnathan D Guest, Nicole Frumento, Alexis Figueroa, Kaitlyn E Clark, Zhenyong Keck, Vanessa M Cowton, Sarah J Cole, Arvind H Patel and 9 more

Abstract read
In one paragraph

Article in Gastroenterology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed.

  1. Article
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  11. The red algaProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Immunological Monitoring in Hepatitis C Virus Controlled Human Infection Model.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Jordan H SalasDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Richard A UrbanowiczSchool of Life Sciences, Faculty of Medicine and Health Sciences, The University of Nottingham, Nottingham, United Kingdom; Wolfson Centre for Global Virus Research, The University of Nottingham, Nottingham, United Kingdom; National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals National Health Service Trust, Nottingham, United Kingdom.
Johnathan D GuestInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland.
Nicole FrumentoDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Alexis FigueroaDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Kaitlyn E ClarkDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Zhenyong KeckDepartment of Pathology, Stanford University School of Medicine, Stanford, California.
Vanessa M CowtonMedical Research Council-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
Sarah J ColeMedical Research Council-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
Arvind H PatelMedical Research Council-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
Thomas R FuerstInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland.
Heidi E DrummerViral Entry and Vaccines Group, Burnet Institute, Melbourne, Victoria, Australia; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia; Department of Microbiology, Monash University, Clayton, Victoria, Australia.
Marian MajorDivision of Viral Products, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland.
Alexander W TarrSchool of Life Sciences, Faculty of Medicine and Health Sciences, The University of Nottingham, Nottingham, United Kingdom; Wolfson Centre for Global Virus Research, The University of Nottingham, Nottingham, United Kingdom; National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals National Health Service Trust, Nottingham, United Kingdom.
Jonathan K BallSchool of Life Sciences, Faculty of Medicine and Health Sciences, The University of Nottingham, Nottingham, United Kingdom; Wolfson Centre for Global Virus Research, The University of Nottingham, Nottingham, United Kingdom; National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals National Health Service Trust, Nottingham, United Kingdom.
Mansun LawDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California.
Brian G PierceInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland.
Steven K H FoungDepartment of Pathology, Stanford University School of Medicine, Stanford, California.
Justin R BaileyDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: jbailey7@jhmi.edu.

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007309 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI COX, ANDREA L · 1985 to 2019
$43.2M
The development and pre-clinical assessment of novel HCV vaccines to generate T and B cell immunityU19AI159822 · NIAID · JOHNS HOPKINS UNIVERSITY · PI COX, ANDREA L · 2021 to 2025
$14.4M
Medical Scientist Training ProgramT32GM136577 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI ANDREA L COX · 2020 to 2026
$13.4M
Scientific CoreU19AI088791 · NIAID · JOHNS HOPKINS UNIVERSITY · PI COX, ANDREA L · 2010 to 2020
$8.2M
Rational design and efficacy testing of vaccines against HCVR01AI168048 · NIAID · UNIV OF MARYLAND, COLLEGE PARK · PI Alexander Andrianov, Thomas R Fuerst · 2022 to 2026
$7.1M
Molecular and structural characterization of broadly neutralizing anti-HCV antibodiesR01AI127469 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Justin Richard Bailey · 2017 to 2026
$6.8M
Structure-Based Vaccine Design for Hepatits C VirusR01AI132213 · NIAID · UNIV OF MARYLAND, COLLEGE PARK · PI ANDRIANOV, ALEXANDER, FOUNG, STEVEN · 2017 to 2021
$6.0M
Understanding human neutralizing antibodies to hepatitis C virusR01AI079031 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI LAW, MANSUN · 2008 to 2017
$4.6M
Novel HCV vaccine antigens targeting conserved neutralizing epitopesU19AI123861 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI ZHU, JIANG · 2016 to 2020
$4.6M
Project 2 - FranceU19AI123862 · NIAID · STANFORD UNIVERSITY · PI BAUMERT, THOMAS F. · 2016 to 2020
$3.9M
Development of standardized immunoassays and virus panels for HCV vaccine researchR24AI158193 · NIAID · JOHNS HOPKINS UNIVERSITY · PI BAILEY, JUSTIN RICHARD, LAW, MANSUN · 2021 to 2023
$1.7M
Graduate Training in VirologyT32AI125186 · NIAID · UNIV OF MARYLAND, COLLEGE PARK · PI SIMON, ANNE ELIZABETH · 2016 to 2020
$1.3M
Medical Research Council G0801169Medical Research Council MC_UU_12014/1Medical Research Council MC_UU_12014/2Medical Research Council MC_UU12014/2Medical Research Council MR/R010307/1NIAID NIH HHS R01 AI079031NIAID NIH HHS R01 AI127469NIAID NIH HHS R01 AI132213NIAID NIH HHS R01 AI168048NIAID NIH HHS R21 AI151353NIAID NIH HHS R24 AI158193NIAID NIH HHS T32 AI125186NIAID NIH HHS U19 AI088791NIAID NIH HHS U19 AI123861NIAID NIH HHS U19 AI123862NIAID NIH HHS U19 AI159822NIGMS NIH HHS T32 GM007309NIGMS NIH HHS T32 GM136577
6 · The paper itself

Abstract

BACKGROUND &

aimsDevelopment 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.

methodsWe 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.

resultsBoth 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.

conclusionsNeutralizing 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.

Indexed as

Antigenic VariationAntigens, ViralBroadly Neutralizing AntibodiesCell Line, TumorHepacivirusHepatitis CHumansImmunogenicity, VaccineNeutralization TestsReproducibility of ResultsVaccine DevelopmentViral Envelope ProteinsViral Hepatitis VaccinesAntigens, ViralBroadly Neutralizing AntibodiesViral Envelope ProteinsViral Hepatitis VaccinesBroadly Neutralizing AntibodiesHepatitis C VirusNeutralizing BreadthVaccine

Identifiers

PMID34655573
PMCPMC8792218

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.