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Record W2346830803 · doi:10.1016/j.celrep.2016.04.026

Antibody Treatment of Ebola and Sudan Virus Infection via a Uniquely Exposed Epitope within the Glycoprotein Receptor-Binding Site

2016· article· en· W2346830803 on OpenAlexafffund
Katie A. Howell, Xiangguo Qiu, Jennifer M. Brannan, Christopher Bryan, Edgar Davidson, Frederick W. Holtsberg, Anna Z. Wec, Sergey Shulenin, Julia E. Biggins, R. Gordon Douglas, Sven Enterlein, Hannah L. Turner, Jesper Pallesen, Charles D. Murin, Shihua He, Andrea Kroeker, Hong Vu, Andrew S. Herbert, Marnie L. Fusco, Elisabeth K. Nyakatura, Jonathan R. Lai, Zhen‐Yong Keck, Steven K. H. Foung, Erica Ollmann Saphire, Larry Zeitlin, Andrew B. Ward, Kartik Chandran, Benjamin J. Doranz, Gary Kobinger, John M. Dye, M. Javad Aman

Bibliographic record

VenueCell Reports · 2016
Typearticle
Languageen
FieldMedicine
TopicViral Infections and Outbreaks Research
Canadian institutionsUniversity of ManitobaPublic Health Agency of Canada
FundersNational Institute of Allergy and Infectious DiseasesNational Science FoundationNational Institutes of HealthPublic Health Agency of CanadaDefense Threat Reduction AgencyDeutscher Akademischer Austauschdienst
KeywordsEbolavirusEpitopeEbola virusVirologyAntibodyMonoclonal antibodyGlycoproteinBiologyVirusImmunologyMolecular biology

Abstract

fetched live from OpenAlex

Previous efforts to identify cross-neutralizing antibodies to the receptor-binding site (RBS) of ebolavirus glycoproteins have been unsuccessful, largely because the RBS is occluded on the viral surface. We report a monoclonal antibody (FVM04) that targets a uniquely exposed epitope within the RBS; cross-neutralizes Ebola (EBOV), Sudan (SUDV), and, to a lesser extent, Bundibugyo viruses; and shows protection against EBOV and SUDV in mice and guinea pigs. The antibody cocktail ZMapp™ is remarkably effective against EBOV (Zaire) but does not cross-neutralize other ebolaviruses. By replacing one of the ZMapp™ components with FVM04, we retained the anti-EBOV efficacy while extending the breadth of protection to SUDV, thereby generating a cross-protective antibody cocktail. In addition, we report several mutations at the base of the ebolavirus glycoprotein that enhance the binding of FVM04 and other cross-reactive antibodies. These findings have important implications for pan-ebolavirus vaccine development and defining broadly protective antibody cocktails.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.056
Threshold uncertainty score0.331

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.023
GPT teacher head0.302
Teacher spread0.280 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations93
Published2016
Admission routes2
Has abstractyes

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