MétaCan
Menu
Back to cohort
Record W3118356453 · doi:10.1101/2021.01.14.426475

N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2

2021· preprint· en· W3118356453 on OpenAlexfundno aff
Matthew McCallum, Anna De Marco, Florian A. Lempp, M. Alejandra Tortorici, Dora Pinto, Alexandra C. Walls, Martina Beltramello, Alex Chen, Zhuoming Liu, Fabrizia Zatta, Samantha K. Zepeda, Julia di Iulio, John E. Bowen, Martin Montiel-Ruiz, Jiayi Zhou, Laura E. Rosen, Siro Bianchi, Barbara Guarino, Chiara Silacci Fregni, Rana Abdelnabi, Shi-Yan Caroline Foo, Paul W. Rothlauf, Louis-Marie Bloyet, Fabio Benigni, Elisabetta Cameroni, Johan Neyts, Agostino Riva, Gyorgy Snell, Amalio Telenti, Sean P. J. Whelan, Herbert W. Virgin, Davide Corti, Matteo Samuele Pizzuto, David Veesler

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2021
Typepreprint
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsnot available
FundersFast GrantsUniversity of WashingtonNational Institute of General Medical SciencesNational Institute of Allergy and Infectious DiseasesNatural Sciences and Engineering Research Council of CanadaBurroughs Wellcome Fund
KeywordsEpitopeVirologyMonoclonal antibodyGlycoproteinAntigenBiologyAntibodyEffectorSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)NeutralizationEpitope mappingCoronavirus disease 2019 (COVID-19)Cell biologyMolecular biologyGeneticsVirusMedicine

Abstract

fetched live from OpenAlex

SARS-CoV-2 entry into host cells is orchestrated by the spike (S) glycoprotein that contains an immunodominant receptor-binding domain (RBD) targeted by the largest fraction of neutralizing antibodies (Abs) in COVID-19 patient plasma. Little is known about neutralizing Abs binding to epitopes outside the RBD and their contribution to protection. Here, we describe 41 human monoclonal Abs (mAbs) derived from memory B cells, which recognize the SARS-CoV-2 S N-terminal domain (NTD) and show that a subset of them neutralize SARS-CoV-2 ultrapotently. We define an antigenic map of the SARS-CoV-2 NTD and identify a supersite recognized by all known NTD-specific neutralizing mAbs. These mAbs inhibit cell-to-cell fusion, activate effector functions, and protect Syrian hamsters from SARS-CoV-2 challenge. SARS-CoV-2 variants, including the 501Y.V2 and B.1.1.7 lineages, harbor frequent mutations localized in the NTD supersite suggesting ongoing selective pressure and the importance of NTD-specific neutralizing mAbs to protective immunity.

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 score0.001
Threshold uncertainty score0.004

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 integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.048
GPT teacher head0.322
Teacher spread0.274 · 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

Citations138
Published2021
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicSARS-CoV-2 and COVID-19 ResearchFrench-language works237,207