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Record W4311140049 · doi:10.1016/j.isci.2022.105783

Molecular basis for antiviral activity of two pediatric neutralizing antibodies targeting SARS-CoV-2 Spike RBD

2022· article· en· W4311140049 on OpenAlexafffund
Yaozong Chen, Jérémie Prévost, Irfan Ullah, Hugo Grisales Romero, Véronique Lisi, William D. Tolbert, Jonathan R. Grover, Shilei Ding, Shang Yu Gong, Guillaume Beaudoin-Bussières, Romain Gasser, Mehdi Benlarbi, Dani Vézina, Sai Priya Anand, Debashree Chatterjee, Guillaume Goyette, Michael W. Grunst, Ziwei Yang, Yuxia Bo, Fei Zhou, Kathie Béland, Xiaoyun Bai, Allison Zeher, Rick Huang, Dung N. Nguyen, Rebekah Sherburn, Di Wu, Grzegorz Piszczek, Bastien Paré, Doreen Matthies, Di Xia, Jonathan Richard, Priti Kumar, Walther Mothes, Marceline Côté, Pradeep D. Uchil, Vincent‐Philippe Lavallée, Martin A. Smith, Marzena Pazgier, Élie Haddad, Andrés Finzi

Bibliographic record

VenueiScience · 2022
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsUniversity of OttawaCentre Hospitalier Universitaire Sainte-JustineUniversité de MontréalMcGill UniversityCentre Hospitalier de l’Université de Montréal
FundersInstitute of Infection and ImmunityBasic Energy SciencesNational Institute of Allergy and Infectious DiseasesNational Institute of General Medical SciencesU.S. Military HIV Research ProgramCanadian Institutes of Health ResearchUniformed Services University of the Health SciencesOffice of ScienceNational Institutes of HealthWorld Meteorological OrganizationNational Research Council CanadaMinistère de l'Économie, de l’Innovation et des Exportations du QuébecFonds de Recherche du Québec - SantéMitacsMinistère de la Santé et des Services sociauxGenome CanadaCanada Foundation for InnovationBiological and Environmental ResearchFondation du CHUMSLAC National Accelerator LaboratoryCRC Health GroupArgonne National LaboratoryU.S. Department of Energy
KeywordsEpitopeAntibodyVirologyNeutralizationIn vivoIn vitroEpitope mappingSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)BiologyChemistryCoronavirus disease 2019 (COVID-19)ImmunologyMedicineBiochemistryGeneticsInfectious disease (medical specialty)

Abstract

fetched live from OpenAlex

Neutralizing antibodies (NAbs) hold great promise for clinical interventions against SARS-CoV-2 variants of concern (VOCs). Understanding NAb epitope-dependent antiviral mechanisms is crucial for developing vaccines and therapeutics against VOCs. Here we characterized two potent NAbs, EH3 and EH8, isolated from an unvaccinated pediatric patient with exceptional plasma neutralization activity. EH3 and EH8 cross-neutralize the early VOCs and mediate strong Fc-dependent effector activity in vitro . Structural analyses of EH3 and EH8 in complex with the receptor-binding domain (RBD) revealed the molecular determinants of the epitope-driven protection and VOC evasion. While EH3 represents the prevalent IGHV3-53 NAb whose epitope substantially overlaps with the ACE2 binding site, EH8 recognizes a narrow epitope exposed in both RBD-up and RBD-down conformations. When tested in vivo, a single-dose prophylactic administration of EH3 fully protected stringent K18-hACE2 mice from lethal challenge with Delta VOC. Our study demonstrates that protective NAbs responses converge in pediatric and adult SARS-CoV-2 patients.

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)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.054
GPT teacher head0.378
Teacher spread0.324 · 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

Citations10
Published2022
Admission routes2
Has abstractyes

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