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Record W4385694287 · doi:10.1016/j.celrep.2023.112942

Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes

2023· article· en· W4385694287 on OpenAlexfundno aff
Rajeshwer S. Sankhala, Vincent Dussupt, Gina Donofrio, Gregory D. Gromowski, Rafael A. De La Barrera, Rafael A. Larocca, Letzibeth Mendez-Rivera, Anna Lee, Misook Choe, Weam I. Zaky, Grace Mantus, Jaime L. Jensen, Wei‐Hung Chen, Neelakshi Gohain, Hongjun Bai, Michael K. McCracken, Rosemarie D. Mason, David J. Leggat, Bonnie M. Slike, Ursula Tran, Ningbo Jian, Peter Abbink, Rebecca Peterson, Érica Araújo Mendes, Rafael Freitas de Oliveira França, Guilherme Amaral Calvet, Ana María Bispo de Filippis, Adrian B. McDermott, Mario Roederer, Mayda Hernandez, Amie Albertus, Edgar Davidson, Benjamin J. Doranz, Morgane Rolland, Merlin L. Robb, Rebecca M. Lynch, Dan H. Barouch, Richard G. Jarman, Stephen J. Thomas, Kayvon Modjarrad, Nelson L. Michael, Shelly J. Krebs, Michael Joyce

Bibliographic record

VenueCell Reports · 2023
Typearticle
Languageen
FieldMedicine
TopicMosquito-borne diseases and control
Canadian institutionsnot available
FundersWalter Reed Army Institute of ResearchBiological and Environmental ResearchDefense Health AgencyNational Institute of Allergy and Infectious DiseasesNational Institute of General Medical SciencesBasic Energy SciencesOffice of ScienceNational Institutes of HealthNational Research Council CanadaUniversity of ChicagoHenry M. Jackson FoundationBrookhaven National LaboratoryArgonne National LaboratoryU.S. Department of EnergyU.S. Department of Defense
KeywordsEpitopeVirologyZika virusMonoclonal antibodyAntibodyBiologyAntigenicityAntigenGlycoproteinEpitope mappingVirusImmunologyMolecular biology

Abstract

fetched live from OpenAlex

Zika virus (ZIKV) is an emerging pathogen that causes devastating congenital defects. The overlapping epidemiology and immunologic cross-reactivity between ZIKV and dengue virus (DENV) pose complex challenges to vaccine design, given the potential for antibody-dependent enhancement of disease. Therefore, classification of ZIKV-specific antibody targets is of notable value. From a ZIKV-infected rhesus macaque, we identify ZIKV-reactive B cells and isolate potent neutralizing monoclonal antibodies (mAbs) with no cross-reactivity to DENV. We group these mAbs into four distinct antigenic groups targeting ZIKV-specific cross-protomer epitopes on the envelope glycoprotein. Co-crystal structures of representative mAbs in complex with ZIKV envelope glycoprotein reveal envelope-dimer epitope and unique dimer-dimer epitope targeting. All four specificities are serologically identified in convalescent humans following ZIKV infection, and representative mAbs from all four groups protect against ZIKV replication in mice. These results provide key insights into ZIKV-specific antigenicity and have implications for ZIKV vaccine, diagnostic, and therapeutic development.

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: Not applicable · Consensus signal: Not applicable
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.482
Threshold uncertainty score0.715

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 head0.021
GPT teacher head0.271
Teacher spread0.250 · 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 designNot applicable
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

Citations17
Published2023
Admission routes1
Has abstractyes

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