Evidence map›Paper›PMID 26238798›Full record

ArticleScientific reports2015

Approaching rational epitope vaccine design for hepatitis C virus with meta-server and multivalent scaffolding.

Linling He, Yushao Cheng, Leopold Kong, Parisa Azadnia, Erick Giang, Justin Kim, Malcolm R Wood, Ian A Wilson, Mansun Law, Jiang Zhu

Abstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing 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

50 citing papers in PubMed.

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  17. [Development approaches for vaccines against hepatitis C virus infections].Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz · 2022
    Review
  18. Article
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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

10 authors.

Linling HeDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037, USA.
Yushao ChengDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037, USA.
Leopold Kong1] Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA [2] International AIDS Vaccine Initiative, Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery [3] Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA.
Parisa AzadniaDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037, USA.
Erick GiangDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037, USA.
Justin KimDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037, USA.
Malcolm R WoodCore Microscopy Facility, The Scripps Research Institute, La Jolla, California 92037, USA.
Ian A Wilson1] Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA [2] International AIDS Vaccine Initiative, Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery [3] Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA.
Mansun LawDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037, USA.
Jiang Zhu1] Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037, USA [2] Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA [3] Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA.

Funding

Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI MCELRATH, MARGARET JULIANA · 2012 to 2018
$131.5M
Understanding human neutralizing antibodies to hepatitis C virusR01AI079031 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI LAW, MANSUN · 2008 to 2017
$4.6M
Dissecting virus neutralizing determinants to guide HCV vaccine developmentR01AI106005 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI LAW, MANSUN · 2014 to 2017
$1.5M
NIAID NIH HHS R01 AI079031NIAID NIH HHS R01 AI106005NIAID NIH HHS UM1 AI100663
6 · The paper itself

Abstract

Development of a prophylactic vaccine against hepatitis C virus (HCV) has been hampered by the extraordinary viral diversity and the poor host immune response. Scaffolding, by grafting an epitope onto a heterologous protein scaffold, offers a possible solution to epitope vaccine design. In this study, we designed and characterized epitope vaccine antigens for the antigenic sites of HCV envelope glycoproteins E1 (residues 314-324) and E2 (residues 412-423), for which neutralizing antibody-bound structures are available. We first combined six structural alignment algorithms in a "scaffolding meta-server" to search for diverse scaffolds that can structurally accommodate the HCV epitopes. For each antigenic site, ten scaffolds were selected for computational design, and the resulting epitope scaffolds were analyzed using structure-scoring functions and molecular dynamics simulation. We experimentally confirmed that three E1 and five E2 epitope scaffolds bound to their respective neutralizing antibodies, but with different kinetics. We then investigated a "multivalent scaffolding" approach by displaying 24 copies of an epitope scaffold on a self-assembling nanoparticle, which markedly increased the avidity of antibody binding. Our study thus demonstrates the utility of a multi-scale scaffolding strategy in epitope vaccine design and provides promising HCV immunogens for further assessment in vivo.

Indexed as

Amino Acid SequenceAntibodies, NeutralizingAntigens, ViralDrug DesignEpitope MappingEpitopesGene ExpressionHEK293 CellsHepacivirusHepatitis CHumansMolecular Dynamics SimulationMolecular Sequence DataProtein BindingRecombinant ProteinsViral Envelope ProteinsAntibodies, NeutralizingAntigens, ViralE1 protein, Hepatitis C virusEpitopesRecombinant ProteinsViral Envelope ProteinsViral Hepatitis Vaccines

Identifiers

PMID26238798
PMCPMC4533164

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Registered trials

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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.