Evidence map›Paper›PMID 38986744›Full record

ArticleJournal of hepatology2024

Recombinant H77C gpE1/gpE2 heterodimer elicits superior HCV cross-neutralisation than H77C gpE2 alone.

Juthika Kundu, Hoa T Le, Michael Logan, Darren Hockman, Abdolamir Landi, Kevin Crawford, Mark Wininger, Janelle Johnson, Joydeb K Kundu, E Alana Tiffney and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of hepatology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. [Progress in clinical research related to viral hepatitis in 2024].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025
    Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Juthika KunduLi Ka Shing Applied Virology Institute, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
Hoa T LeLi Ka Shing Applied Virology Institute, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
Michael LoganLi Ka Shing Applied Virology Institute, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
Darren HockmanLi Ka Shing Applied Virology Institute, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
Abdolamir LandiLi Ka Shing Applied Virology Institute, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
Kevin CrawfordLi Ka Shing Applied Virology Institute, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
Mark WiningerLi Ka Shing Applied Virology Institute, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
Janelle JohnsonLi Ka Shing Applied Virology Institute, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
Joydeb K KunduLi Ka Shing Applied Virology Institute, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
E Alana TiffneyDept of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.
Richard A UrbanowiczDept of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.
Jonathan K BallWolfson Centre for Global Virus Infections, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom; Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Justin R BaileyJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jens BukhCopenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Mansun LawDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, USA.
Steven FoungDepartment of Pathology, Stanford University, Palo Alto, California, USA.
D Lorne TyrrellLi Ka Shing Applied Virology Institute, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
Michael HoughtonLi Ka Shing Applied Virology Institute, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada. Electronic address: michael.houghton@ualberta.ca.
John Lokman LawLi Ka Shing Applied Virology Institute, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.

Funding

Vaccine against HCV in nonhuman primatesU19AI159840 · NIAID · STANFORD UNIVERSITY · PI FOUNG, STEVEN · 2021 to 2025
$11.9M
NIAID NIH HHS U19 AI159840
6 · The paper itself

Abstract

BACKGROUND &

aimsAn optimal HCV vaccine requires the induction of antibodies that neutralise the infectivity of many heterogenous viral isolates. In this study, we have focused on determining the optimal recombinant envelope glycoprotein component to elicit cross-neutralising antibodies against global HCV genotypes. We compared the immunoreactivity and antigenicity of the HCV genotype 1a strain H77C-derived envelope glycoprotein heterodimer gpE1/gpE2 with that of recombinant gpE2 alone.

methodsCharacterisation of the envelope glycoproteins was accomplished by determining their ability to bind to a panel of broadly cross-neutralising monoclonal antibodies. Immunogenicity was determined by testing the ability of vaccine antisera to neutralise the infectivity in vitro of a panel of pseudotyped HCV particles in which gpE1/gpE2 derived from representative isolates of the major global HCV genotypes were displayed.

resultsgpE1/gpE2 binds to more diverse broadly cross-neutralising antibodies than gpE2 alone and elicits a broader profile of cross-neutralising antibodies in animals, especially against more heterologous, non-1a genotypes. While not all heterologous HCV strains can be potently inhibited in vitro by gpE1/gpE2 antisera derived from a single HCV strain, the breadth of heterologous cross-neutralisation is shown to be substantial.

conclusionsOur work supports the inclusion of gpE1/gpE2 in an HCV vaccine in order to maximise the cross-neutralisation of heterogenous HCV isolates. Our data also offers future directions in formulating a cocktail of gpE1/gpE2 antigens from a small selection of HCV genotypes to further enhance cross-neutralisation of global HCV strains and hopefully advance the development of a globally effective HCV vaccine. IMPACT AND IMPLICATIONS: An HCV vaccine is urgently required to prevent the high global incidence of HCV infection and disease. Since HCV is a highly heterogeneous virus, it is desirable for a vaccine to elicit antibodies that neutralise the infectivity of most global strains. To this end, we have compared the immunoreactivity and antigenicity of recombinant H77C E1E2 heterodimer with that of H77C E2 alone and show that the former exhibits more cross-neutralising epitopes and demonstrates a broader cross-neutralisation profile in vitro. In addition, our data suggests a way to further broaden cross-neutralisation using a combination of E1E2 antigens derived from a few different HCV clades. Our work is relevant for the development of an effective global HCV vaccine.

Indexed as

HepacivirusViral Envelope ProteinsViral Hepatitis VaccinesAnimalsAntibodies, NeutralizingCross ReactionsGenotypeHepatitis CHepatitis C AntibodiesHumansMiceRecombinant ProteinsAntibodies, NeutralizingE1 protein, Hepatitis C virusglycoprotein E2, Hepatitis C virusHepatitis C AntibodiesRecombinant ProteinsViral Envelope ProteinsViral Hepatitis Vaccinesantibodycross-neutralisationHCVvaccine

Identifiers

PMID38986744
PMCPMC11830426

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.