Evidence map›Paper›PMID 34652943›Full record

ArticleScience advances2021

Designed, highly expressing, thermostable dengue virus 2 envelope protein dimers elicit quaternary epitope antibodies.

Stephan T Kudlacek, Stefan Metz, Devina Thiono, Alexander M Payne, Thanh T N Phan, Shaomin Tian, Lawrence J Forsberg, Jack Maguire, Ian Seim, Shu Zhang and 10 more

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 1 pooled it
7.3field-weighted citation impact, top 2% 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

44 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. ApoJ regulates endothelial lipase activity and stability.Protein science : a publication of the Protein Society · 2026
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  7. Keratinocytes: pleiotropic orchestrators of cutaneous immunity and Inflammation - Emerging therapeutic paradigms in dermatological pathologies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  8. Article
  9. Article
  10. Review
  11. Shared PRAME epitopes are T-cell targets in NUT carcinoma.Journal for immunotherapy of cancer · 2026
    Article
  12. Review
  13. Article
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  15. 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

20 authors at 2 institutions in 1 country.

Stephan T KudlacekDepartment of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27514, USA.ORCID 0000-0002-0029-9984
Stefan MetzDepartment of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27514, USA.ORCID 0000-0002-9249-2844
Devina ThionoDepartment of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27514, USA.ORCID 0000-0002-8330-0396
Alexander M PayneDepartment of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27514, USA.ORCID 0000-0003-0947-0191
Thanh T N PhanDepartment of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27514, USA.ORCID 0000-0002-2727-6133
Shaomin TianDepartment of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27514, USA.ORCID 0000-0001-5220-3887
Lawrence J ForsbergDepartment of Pharmacology, University of North Carolina, Chapel Hill, NC 27514, USA.ORCID 0000-0002-4787-9847
Jack MaguireDepartment of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27514, USA.ORCID 0000-0003-0581-6431
Ian SeimCurriculum in Bioinformatics and Computational Biology, University of North Carolina, Chapel Hill, NC 27514, USA.ORCID 0000-0001-9719-2552
Shu ZhangDepartment of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27514, USA.ORCID 0000-0002-0185-4126
Ashutosh TripathyDepartment of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27514, USA.
Joseph HarrisonDepartment of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27514, USA.ORCID 0000-0002-2118-6524
Nathan I NicelyDepartment of Pharmacology, University of North Carolina, Chapel Hill, NC 27514, USA.ORCID 0000-0002-0025-2377
Sandrine SomanViral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Michael K McCrackenViral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.ORCID 0000-0002-4035-5485
Gregory D GromowskiViral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Richard G JarmanViral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.ORCID 0000-0002-5765-0173
Lakshmanane PremkumarDepartment of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27514, USA.ORCID 0000-0002-1736-1350
Aravinda M de SilvaDepartment of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27514, USA.ORCID 0000-0003-3317-5950
Brian KuhlmanDepartment of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27514, USA.ORCID 0000-0003-4907-9699
University of North Carolina at Chapel Hill · USWalter Reed Army Institute of Research · US

Funding

Protein Expression/Dengue Virology CoreU19AI109784 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI TING, JENNY P · 2014 to 2018
$20.8M
GPU workstation for deep learning-based protein design and cryo-EM data processingR35GM131923 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BRIAN A KUHLMAN · 2019 to 2026
$6.1M
Molecular Basis of Flavivirus Cross-Neutralization by Human AntibodiesR01AI107731 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DESILVA, ARAVINDA M. · 2013 to 2022
$5.3M
MOLECULAR AND CELLULAR BIOPHYSICS TRAINING PROGRAMT32GM008570 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KUHLMAN, BRIAN A, SLEP, KEVIN C · 1995 to 2022
$5.1M
NIAID NIH HHS R01 AI107731NIAID NIH HHS U19 AI109784NIGMS NIH HHS R35 GM131923NIGMS NIH HHS T32 GM008570
6 · The paper itself

Abstract

Dengue virus (DENV) is a worldwide health burden, and a safe vaccine is needed. Neutralizing antibodies bind to quaternary epitopes on DENV envelope (E) protein homodimers. However, recombinantly expressed soluble E proteins are monomers under vaccination conditions and do not present these quaternary epitopes, partly explaining their limited success as vaccine antigens. Using molecular modeling, we found DENV2 E protein mutations that induce dimerization at low concentrations (<100 pM) and enhance production yield by more than 50-fold. Cross-dimer epitope antibodies bind to the stabilized dimers, and a crystal structure resembles the wild-type (WT) E protein bound to a dimer epitope antibody. Mice immunized with the stabilized dimers developed antibodies that bind to E dimers and not monomers and elicited higher levels of DENV2-neutralizing antibodies compared to mice immunized with WT E antigen. Our findings demonstrate the feasibility of using structure-based design to produce subunit vaccines for dengue and other flaviviruses.

Identifiers

PMID34652943
PMCPMC8519570
OpenAlexW3207515583

What OpenQuestion holds

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LicenceCC BY
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.