Evidence map›Paper›PMID 22499787›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2012

Identification of human neutralizing antibodies that bind to complex epitopes on dengue virions.

Ruklanthi de Alwis, Scott A Smith, Nicholas P Olivarez, William B Messer, Jeremy P Huynh, Wahala M P B Wahala, Laura J White, Michael S Diamond, Ralph S Baric, James E Crowe and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 262 papers.

0numbers the graph read from it
0cells of the map it votes in
262citing papers in PubMed
34.6field-weighted citation impact, top 1% 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

262 citing papers in PubMed, 392 citations in OpenAlex.

  1. Viral genetic diversity and protective efficacy of a tetravalent dengue vaccine in two phase 3 trials.Proceedings of the National Academy of Sciences of the United States of America · 2018
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202 more citing papers are in PubMed but not listed here.

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

11 authors at 4 institutions in 3 countries.

Ruklanthi de AlwisDepartment of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Scott A Smith
Nicholas P Olivarez
William B Messer
Jeremy P Huynh
Wahala M P B Wahala
Laura J White
Michael S Diamond
Ralph S Baric
James E Crowe
Aravinda M de Silva
University of North Carolina at Chapel Hill · USBipar · FRPediatrics and Genetics · USVanderbilt University Medical Center · US

Funding

Yessinia autotransporters (Yaps): Structure, function, and host responseU54AI057157 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WEISS, DAVID S · 2003 to 2013
$91.4M
Key determinants of dengue virus neutralization by naturally occurring human mAbsK08AI103038 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI SMITH, SCOTT ALAN · 2012 to 2016
$631k
NIAID NIH HHS K08 AI103038NIAID NIH HHS U54 AI057157
6 · The paper itself

Abstract

Dengue is a mosquito-borne flavivirus that is spreading at an unprecedented rate and has developed into a major health and economic burden in over 50 countries. Even though infected individuals develop potent and long-lasting serotype-specific neutralizing antibodies (Abs), the epitopes engaged by human neutralizing Abs have not been identified. Here, we demonstrate that the dengue virus (DENV)-specific serum Ab response in humans consists of a large fraction of cross-reactive, poorly neutralizing Abs and a small fraction of serotype-specific, potently inhibitory Abs. Although many mouse-generated, strongly neutralizing monoclonal antibodies (mAbs) recognize epitopes that are present on recombinant DENV envelope (E) proteins, unexpectedly, the majority of neutralizing Abs in human immune sera bound to intact virions but not to the ectodomain of purified soluble E proteins. These conclusions with polyclonal Abs were confirmed with newly generated human mAbs derived from DENV-immune individuals. Two of three strongly neutralizing human mAbs bound to E protein epitopes that were preserved on the virion but not on recombinant E (rE) protein. We propose that humans produce Abs that neutralize DENV infection by binding a complex, quaternary structure epitope that is expressed only when E proteins are assembled on a virus particle. Mapping studies indicate that this epitope has a footprint that spans adjacent E protein dimers and includes residues at the hinge between domains I and II of E protein. These results have significant implications for the DENV Ab and vaccine field.

Indexed as

Amino Acid SequenceAnimalsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralAntibody SpecificityChlorocebus aethiopsDengueDengue VirusEnzyme-Linked Immunosorbent AssayEpitopesHumansImmune SeraMacaca mulattaModels, MolecularMolecular Sequence DataAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralEpitopesE protein TH Sman, Dengue virusImmune SeraRecombinant ProteinsViral Envelope Proteins

Identifiers

PMID22499787
PMCPMC3358852
OpenAlexW2017577931

What OpenQuestion holds

Textmetadata
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.