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Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs

2015· article· en· W807802234 on OpenAlexaff
Marnie L. Fusco, Takao Hashiguchi, Robyn Cassan, Julia E. Biggins, Charles D. Murin, Kelly L. Warfield, Sheng Li, Frederick W. Holtsberg, Sergey Shulenin, Hong Vu, Gene G. Olinger, Do H. Kim, Kevin J. Whaley, Larry Zeitlin, Andrew B. Ward, Cory L. Nykiforuk, M. Javad Aman, Jody Berry, Erica Ollmann Saphire

Bibliographic record

VenuePLoS Pathogens · 2015
Typearticle
Languageen
FieldMedicine
TopicViral Infections and Outbreaks Research
Canadian institutionsEmergent BioSolutions (Canada)
FundersNational Institute of Allergy and Infectious DiseasesJapan Society for the Promotion of ScienceBurroughs Wellcome FundUehara Memorial FoundationNational Science Foundation
KeywordsMarburg virusEbola virusVirologyMonoclonal antibodyEpitopeGlycoproteinImmunizationMucinAntibodyBiologyFiloviridaeVirusEbola vaccineEbolavirusRecombinant DNAImmunologyParamyxoviridaeMolecular biologyViral diseaseGenetics

Abstract

fetched live from OpenAlex

The filoviruses, which include the marburg- and ebolaviruses, have caused multiple outbreaks among humans this decade. Antibodies against the filovirus surface glycoprotein (GP) have been shown to provide life-saving therapy in nonhuman primates, but such antibodies are generally virus-specific. Many monoclonal antibodies (mAbs) have been described against Ebola virus. In contrast, relatively few have been described against Marburg virus. Here we present ten mAbs elicited by immunization of mice using recombinant mucin-deleted GPs from different Marburg virus (MARV) strains. Surprisingly, two of the mAbs raised against MARV GP also cross-react with the mucin-deleted GP cores of all tested ebolaviruses (Ebola, Sudan, Bundibugyo, Reston), but these epitopes are masked differently by the mucin-like domains themselves. The most efficacious mAbs in this panel were found to recognize a novel "wing" feature on the GP2 subunit that is unique to Marburg and does not exist in Ebola. Two of these anti-wing antibodies confer 90 and 100% protection, respectively, one hour post-exposure in mice challenged with MARV.

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 score0.176
Threshold uncertainty score0.532

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 head0.030
GPT teacher head0.292
Teacher spread0.262 · 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

Citations57
Published2015
Admission routes1
Has abstractyes

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