Evidence map›Paper›PMID 32494617›Full record

ArticleScience advances2020

Proof of concept for rational design of hepatitis C virus E2 core nanoparticle vaccines.

Linling He, Netanel Tzarum, Xiaohe Lin, Benjamin Shapero, Cindy Sou, Colin J Mann, Armando Stano, Lei Zhang, Kenna Nagy, Erick Giang and 3 more

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2020. 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
5.5field-weighted citation impact, top 3% of its field
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, 67 citations in OpenAlex.

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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

13 authors at 1 institution in 1 country.

Linling HeDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0001-8846-5352
Netanel TzarumDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0001-6401-1356
Xiaohe LinDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Benjamin ShaperoDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0002-4328-0298
Cindy SouDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Colin J MannDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0003-0949-2075
Armando StanoDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Lei ZhangDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Kenna NagyDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0002-3772-3160
Erick GiangDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Mansun LawDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0002-8934-9756
Ian A WilsonDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0002-6469-2419
Jiang ZhuDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0003-0259-7157
Scripps Research Institute · US

Funding

UC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3M
VirologyP30AI036214 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI David Mitchell Smith · 1994 to 2026
$78.4M
ZWITTERION SURFACTANT DDMAB FOR IMPROV STABIL OF PROTEINP41RR001209 · NCRR · STANFORD UNIVERSITY · PI SCOTT, EMILY E · 1985 to 2011
$38.9M
X-ray Absorption Spectroscopy (XAS) pp.711-759P41GM103393 · NIGMS · STANFORD UNIVERSITY · PI HODGSON, KEITH O · 2012 to 2019
$30.6M
Pushing the envelope: Optimizing vaccine display of flexibly linked HIV Env trimer immunogensP01AI124337 · NIAID · INTERNATIONAL AIDS VACCINE INITIATIVE · PI ZHU, JIANG · 2016 to 2020
$12.2M
Uncleaved prefusion-optimized trimers on nanoparticles as HIV vaccinesR01AI140844 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI ZHU, JIANG · 2019 to 2023
$4.9M
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
Rational design and B cell responses of HIV epitope vaccinesR01AI129698 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI ZHU, JIANG · 2017 to 2021
$3.2M
Structure and function of Hepacivirus envelope glycoproteinR01AI123365 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI LAW, MANSUN, WILSON, IAN A · 2016 to 2020
$3.1M
Dissecting virus neutralizing determinants to guide HCV vaccine developmentR01AI106005 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI LAW, MANSUN · 2014 to 2017
$1.5M
Dissecting virus neutralizing determinants to guide HCV vaccine developmentR56AI106005 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI LAW, MANSUN · 2013 to 2013
$793k
NCATS NIH HHS UL1 TR001442NCRR NIH HHS P41 RR001209NIAID NIH HHS P01 AI124337NIAID NIH HHS P30 AI036214NIAID NIH HHS R01 AI079031NIAID NIH HHS R01 AI106005NIAID NIH HHS R01 AI123365NIAID NIH HHS R01 AI129698NIAID NIH HHS R01 AI140844NIAID NIH HHS R56 AI106005NIAID NIH HHS U19 AI123861NIGMS NIH HHS P41 GM103393
6 · The paper itself

Abstract

Hepatitis C virus (HCV) envelope glycoproteins E1 and E2 are responsible for cell entry, with E2 being the major target of neutralizing antibodies (NAbs). Here, we present a comprehensive strategy for B cell-based HCV vaccine development through E2 optimization and nanoparticle display. We redesigned variable region 2 in a truncated form (tVR2) on E2 cores derived from genotypes 1a and 6a, resulting in improved stability and antigenicity. Crystal structures of three optimized E2 cores with human cross-genotype NAbs (AR3s) revealed how the modified tVR2 stabilizes E2 without altering key neutralizing epitopes. We then displayed these E2 cores on 24- and 60-meric nanoparticles and achieved substantial yield and purity, as well as enhanced antigenicity. In mice, these nanoparticles elicited more effective NAb responses than soluble E2 cores. Next-generation sequencing (NGS) defined distinct B cell patterns associated with nanoparticle-induced antibody responses, which target the conserved neutralizing epitopes on E2 and cross-neutralize HCV genotypes.

Indexed as

Hepatitis CNanoparticlesVaccinesAnimalsAntibodies, NeutralizingEpitopesHepacivirusHepatitis C AntibodiesMiceAntibodies, NeutralizingEpitopesHepatitis C AntibodiesVaccines

Identifiers

PMID32494617
PMCPMC7159917
OpenAlexW3016855528

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

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.