Evidence map›Paper›PMID 30928493›Full record

ReviewJournal of molecular biology2019

Potent Neutralization of Staphylococcal Enterotoxin B In Vivo by Antibodies that Block Binding to the T-Cell Receptor.

Gang Chen, Hatice Karauzum, Hua Long, Danielle Carranza, Frederick W Holtsberg, Katie A Howell, Laura Abaandou, Bojie Zhang, Nick Jarvik, Wei Ye and 6 more

Open access · greenAbstract readReview
In one paragraph

Review in Journal of molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.0field-weighted citation impact, top 26% 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

15 citing papers in PubMed, 24 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

16 authors at 3 institutions in 2 countries.

Gang ChenBanting and Best Department of Medical Research, Department of Molecular Genetics, and the Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Hatice KarauzumIntegrated Biotherapeutics, Inc., Rockville, MD 20850, USA.
Hua LongBanting and Best Department of Medical Research, Department of Molecular Genetics, and the Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Danielle CarranzaBanting and Best Department of Medical Research, Department of Molecular Genetics, and the Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Frederick W HoltsbergIntegrated Biotherapeutics, Inc., Rockville, MD 20850, USA.
Katie A HowellIntegrated Biotherapeutics, Inc., Rockville, MD 20850, USA.
Laura AbaandouIntegrated Biotherapeutics, Inc., Rockville, MD 20850, USA.
Bojie ZhangDepartment of Chemistry, Washington University in St. Louis, St Louis, MO 63130, USA.
Nick JarvikBanting and Best Department of Medical Research, Department of Molecular Genetics, and the Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Wei YeBanting and Best Department of Medical Research, Department of Molecular Genetics, and the Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Grant C LiaoIntegrated Biotherapeutics, Inc., Rockville, MD 20850, USA.
Michael L GrossDepartment of Chemistry, Washington University in St. Louis, St Louis, MO 63130, USA; Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
Daisy W LeungDepartment of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
Gaya K AmarasingheDepartment of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
M Javad AmanIntegrated Biotherapeutics, Inc., Rockville, MD 20850, USA. Electronic address: javad@integratedbiotherapeutics.com.
Sachdev S SidhuBanting and Best Department of Medical Research, Department of Molecular Genetics, and the Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada. Electronic address: sachdev.sidhu@utoronto.ca.
Integrated BioTherapeutics (United States) · USUniversity of Toronto · CAWashington University in St. Louis · US

Funding

TrainingP41GM103422 · NIGMS · WASHINGTON UNIVERSITY · PI YARASHESKI, KEVIN E · 2012 to 2019
$12.0M
Multivalent Toxoid Vaccine for recurrent Staphylococccus aureus diseaseR01AI111205 · NIAID · INTEGRATED BIOTHERAPEUTICS, INC. · PI M Javad Aman · 2015 to 2026
$6.9M
Therapeutic Human Monoclonal Antibodies Against Staphylococcal Enterotoxin B (SEBU01AI078023 · NIAID · INTEGRATED BIOTHERAPEUTICS, INC. · PI AMAN, M JAVAD · 2008 to 2012
$5.4M
NIAID NIH HHS R01 AI111205NIAID NIH HHS U01 AI078023NIGMS NIH HHS P41 GM103422
6 · The paper itself

Abstract

To develop an antibody (Ab) therapeutic against staphylococcal enterotoxin B (SEB), a potential incapacitating bioterrorism agent and a major cause of food poisoning, we developed a "class T" anti-SEB neutralizing Ab (GC132) targeting an epitope on SEB distinct from that of previously developed "class M" Abs. A systematic engineering approach was applied to affinity-mature Ab GC132 to yield an optimized therapeutic candidate (GC132a) with sub-nanomolar binding affinity. Mapping of the binding interface by hydrogen-deuterium exchange coupled to mass spectrometry revealed that the class T epitope on SEB overlapped with the T-cell receptor binding site, whereas other evidence suggested that the class M epitope overlapped with the binding site for the major histocompatibility complex. In the IgG format, GC132a showed ∼50-fold more potent toxin-neutralizing efficacy than the best class M Ab in vitro, and fully protected mice from lethal challenge in a toxic shock post-exposure model. We also engineered bispecific Abs (bsAbs) that bound tetravalently by utilizing two class M binding sites and two class T binding sites. The bsAbs displayed enhanced toxin neutralization efficacy compared with the respective monospecific Ab subunits as well as a mixture of the two, indicating that enhanced efficacy was due to heterotypic tetravalent binding to two non-overlapping epitopes on SEB. Together, these results suggest that class T anti-SEB Ab GC132a is an excellent candidate for clinical development and for bsAb engineering.

Indexed as

AnimalsAntibodies, BacterialAntibodies, BispecificAntibodies, NeutralizingCell Surface Display TechniquesEnterotoxinsHumansMass SpectrometryModels, BiologicalProtein EngineeringReceptors, Antigen, T-CellAntibodies, BacterialAntibodies, BispecificAntibodies, Neutralizingenterotoxin B, staphylococcalEnterotoxinsReceptors, Antigen, T-Cellhydrogen–deuterium exchange coupled to mass spectrometryphage displayprotein engineeringSEB toxinsynthetic antibody

Identifiers

PMID30928493
PMCPMC6764902
OpenAlexW2922721653

What OpenQuestion holds

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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.