Evidence map›Paper›PMID 29215033›Full record

ArticleScientific reports2017

Transplantation of a quaternary structure neutralizing antibody epitope from dengue virus serotype 3 into serotype 4.

Douglas G Widman, Ellen Young, Usha Nivarthi, Jesica A Swanstrom, Scott R Royal, Boyd L Yount, Kari Debbink, Matthew Begley, Stephanie Marcet, Anna Durbin and 3 more

Abstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

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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.

Douglas G WidmanDepartment of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, USA.
Ellen YoungDepartment of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, USA.
Usha NivarthiDepartment of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Jesica A SwanstromDepartment of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, USA.
Scott R RoyalDepartment of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, USA.ORCID 0000-0001-5724-0644
Boyd L YountDepartment of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, USA.
Kari DebbinkDepartment of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Matthew BegleyDepartment of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, USA.
Stephanie MarcetDepartment of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, USA.
Anna DurbinCenter for Immunization Research, Department for International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Aravinda M de SilvaDepartment of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
William B MesserDepartment of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, USA.
Ralph S BaricDepartment of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, USA. rbaric@email.unc.edu.

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
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
NCI NIH HHS P30 CA016086NIAID NIH HHS P01 AI106695NIAID NIH HHS R01 AI107731
6 · The paper itself

Abstract

Dengue vaccine trials have revealed deficits in our understanding of the mechanisms of protective immunity, demonstrating a need to measure epitope-specific antibody responses against each DENV serotype. HmAb 5J7 binds to a complex, 3-monomer spanning quaternary epitope in the DENV3 envelope (E) protein, but it is unclear whether all interactions are needed for neutralization. Structure guided design and reverse genetics were used to sequentially transplant larger portions of the DENV3-specific 5J7 mAb epitope into dengue virus serotype 4 (DENV4). We observed complete binding and neutralization only when the entire 3 monomer spanning epitope was transplanted into DENV4, providing empirical proof that cooperative monomer-hmAb 5J7 interactions maximize activity. The rDENV4/3 virus containing the most expanded 5J7 epitope was also significantly more sensitive than WT DENV4 to neutralization by DENV3 primary immune sera. We conclude that the hinge-spanning region of the 5J7 quaternary epitope is a target for serotype-specific neutralizing antibodies after DENV3 infection.

Indexed as

Amino Acid SequenceAnimalsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralChlorocebus aethiopsDengueDengue VirusEpitopesHumansNeutralization TestsProtein Structure, QuaternarySequence HomologySerogroupU937 CellsVero CellsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralEpitopesViral Envelope Proteins

Identifiers

PMID29215033
PMCPMC5719398

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.