Evidence map›Paper›PMID 37725085›Full record

ArticleeLife2023

Evolution of a functionally intact but antigenically distinct DENV fusion loop.

Rita M Meganck, Deanna Zhu, Stephanie Dong, Lisa J Snoderly-Foster, Yago R Dalben, Devina Thiono, Laura J White, Arivianda M DeSilva, Ralph S Baric, Longping V Tse

Open access · goldAbstract read
In one paragraph

Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 31% 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

5 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
  2. Article
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  4. Review
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Rita M MeganckDepartment of Molecular Microbiology and Immunology, Saint Louis University, Saint Louis, United States.
Deanna ZhuDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, United States.
Stephanie DongDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, United States.
Lisa J Snoderly-FosterDepartment of Molecular Microbiology and Immunology, Saint Louis University, Saint Louis, United States.
Yago R DalbenDepartment of Molecular Microbiology and Immunology, Saint Louis University, Saint Louis, United States.
Devina ThionoDepartment of Microbiology, University of North Carolina at Chapel Hill, Chapel Hill, United States.ORCID 0000-0002-8330-0396
Laura J WhiteDepartment of Microbiology, University of North Carolina at Chapel Hill, Chapel Hill, United States.
Arivianda M DeSilvaDepartment of Microbiology, University of North Carolina at Chapel Hill, Chapel Hill, United States.ORCID 0000-0003-3317-5950
Ralph S BaricDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, United States.
Longping V TseDepartment of Molecular Microbiology and Immunology, Saint Louis University, Saint Louis, United States.ORCID 0000-0001-7582-8396
University of North Carolina at Chapel Hill · USSaint Louis University · ES

Funding

T Cell Responses Following DENV Natural Infections and Live-Attenuated Dengue Virus VaccinationP01AI106695 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI Eva Harris · 2015 to 2026
$34.1M
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
Age in dengue antibody response and risk after primary natural infectionF30AI160898 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ZHU, DEANNA · 2021 to 2024
$170k
NIAID NIH HHS F30 AI160898NIAID NIH HHS P01 AI106695NIAID NIH HHS R01 AI107731
6 · The paper itself

Abstract

A hallmark of dengue virus (DENV) pathogenesis is the potential for antibody-dependent enhancement, which is associated with deadly DENV secondary infection, complicates the identification of correlates of protection, and negatively impacts the safety and efficacy of DENV vaccines. Antibody-dependent enhancement is linked to antibodies targeting the fusion loop (FL) motif of the envelope protein, which is completely conserved in mosquito-borne flaviviruses and required for viral entry and fusion. In the current study, we utilized saturation mutagenesis and directed evolution to engineer a functional variant with a mutated FL (D2-FL), which is not neutralized by FL-targeting monoclonal antibodies. The FL mutations were combined with our previously evolved prM cleavage site to create a mature version of D2-FL (D2-FLM), which evades both prM- and FL-Abs but retains sensitivity to other type-specific and quaternary cross-reactive (CR) Abs. CR serum from heterotypic (DENV4)-infected non-human primates (NHP) showed lower neutralization titers against D2-FL and D2-FLM than isogenic wildtype DENV2 while similar neutralization titers were observed in serum from homotypic (DENV2)-infected NHP. We propose D2-FL and D2-FLM as valuable tools to delineate CR Ab subtypes in serum as well as an exciting platform for safer live-attenuated DENV vaccines suitable for naïve individuals and children.

Indexed as

CulicidaeVaccinesAnimalsAntibodies, MonoclonalCross ReactionsEngineeringAntibodies, MonoclonalVaccinesdengue virusevolutionfusion loopinfectious diseasemicrobiologysaturation mutagenesisserumvaccineviruses

Identifiers

PMID37725085
PMCPMC10508882
OpenAlexW4384108566

What OpenQuestion holds

Textmetadata
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.