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Record W2885311140 · doi:10.1101/395525

Human antibody cocktail deploys multiple functions to confer pan-ebolavirus protection

2018· preprint· en· W2885311140 on OpenAlexafffund
Anna Z. Wec, Zachary A. Bornholdt, Shihua He, Andrew S. Herbert, Eileen C. Goodwin, Ariel S. Wirchnianski, Bronwyn M. Gunn, Zirui Zhang, Wenjun Zhu, Guodong Liu, Dafna M. Abelson, Crystal L. Moyer, Rohit K. Jangra, Rebekah M. James, Russell R. Bakken, Natasha Bohorova, Ognian Bohorov, Do H. Kim, Michael Pauly, Jesús Velasco, Robert H. Bortz, Kevin J. Whaley, Tracey Goldstein, Simon J. Anthony, Galit Alter, Laura M. Walker, John M. Dye, Larry Zeitlin, Xiangguo Qiu, Kartik Chandran

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2018
Typepreprint
Languageen
FieldMedicine
TopicViral Infections and Outbreaks Research
Canadian institutionsUniversity of ManitobaPublic Health Agency of Canada
FundersDefense Threat Reduction AgencyNational Institutes of HealthPublic Health AgencyPublic Health Agency of CanadaU.S. Department of Defense
KeywordsEbolavirusEbola virusVirologyMonoclonal antibodyAntibodyBiologyNeutralizationVirusImmunology

Abstract

fetched live from OpenAlex

During the unprecedented 2013–2016 Ebola virus disease (EVD) epidemic in Western Africa and in its aftermath, the passive administration of monoclonal antibodies (mAbs) emerged as a promising treatment approach 1–7 . However, all antibody-based therapeutics currently in advanced development are specific for a single member of the Ebolavirus genus, Ebola virus (EBOV), and ineffective against divergent outbreak-causing ebolaviruses, including Bundibugyo virus (BDBV) and Sudan virus (SUDV) 2,3,5,7 . Here we advance MBP134, a cocktail of two broadly neutralizing human mAbs targeting the filovirus surface glycoprotein, GP, as a candidate pan-ebolavirus therapeutic. One component of this cocktail is a pan-ebolavirus neutralizing mAb, ADI-15878, isolated from a human EVD survivor 8,9 . The second, ADI-23774, was derived by affinity maturation of a human mAb 8,9 via yeast display to enhance its potency against SUDV. MBP134 afforded exceptionally potent pan-ebolavirus neutralization in vitro and demonstrated greater protective efficacy than ADI-15878 alone in the guinea pig model of lethal EBOV challenge. A second-generation cocktail, MBP134 AF , engineered to effectively harness natural killer (NK) cells afforded additional, unprecedented improvements in protective efficacy against EBOV and SUDV in guinea pigs relative to both its precursor and to any mAbs or mAb cocktails tested previously. MBP134 AF is a best-in-class mAb cocktail suitable for evaluation as a pan-ebolavirus therapeutic in nonhuman primates.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.041
GPT teacher head0.311
Teacher spread0.270 · 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 source (direct Gemma or distilled Codex), 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

Citations0
Published2018
Admission routes2
Has abstractyes

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