Evidence map›Paper›PMID 36146867›Full record

ArticleViruses2022

Receptor-Binding Domain (RBD) Antibodies Contribute More to SARS-CoV-2 Neutralization When Target Cells Express High Levels of ACE2.

Ariana Ghez Farrell, Bernadeta Dadonaite, Allison J Greaney, Rachel Eguia, Andrea N Loes, Nicholas M Franko, Jennifer Logue, Juan Manuel Carreño, Anass Abbad, Helen Y Chu and 2 more

Open access · goldAbstract read
In one paragraph

Article in Viruses, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.8field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 39 citations in OpenAlex.

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  7. Outstanding Contributions to Aerosol Pulmonary Drug Delivery.Kona : powder science and technology in Japan · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 1 country.

Ariana Ghez FarrellBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.ORCID 0000-0002-1389-0992
Bernadeta DadonaiteBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Allison J GreaneyBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Rachel EguiaBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Andrea N LoesBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Nicholas M FrankoDivision of Allergy and Infectious Diseases, University of Washington, Seattle, WA 98109, USA.
Jennifer LogueDivision of Allergy and Infectious Diseases, University of Washington, Seattle, WA 98109, USA.ORCID 0000-0002-7889-8960
Juan Manuel CarreñoDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0002-9039-9275
Anass AbbadDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Helen Y ChuDivision of Allergy and Infectious Diseases, University of Washington, Seattle, WA 98109, USA.
Kenneth A MatreyekDepartment of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.ORCID 0000-0001-9149-551X
Jesse D BloomBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.ORCID 0000-0003-1267-3408
University of Washington · USFred Hutch Cancer Center · USHoward Hughes Medical Institute · USIcahn School of Medicine at Mount Sinai · USCase Western Reserve University · US

Funding

NIAID Centers of Excellence for Influenza Research and Response: Universal Influenza Vaccine Research Activities75N93021C00015 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HENSLEY, SCOTT · 2021 to 2025
$50.7M
Prospectively characterizing the functional and antigenic effects of mutations to viral entry proteinsR01AI141707 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BLOOM, JESSE D · 2018 to 2022
$2.1M
Recombinant DNA technologies for multiplex genetic assays in human cellsR35GM142886 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI MATREYEK, KENNETH A · 2021 to 2025
$2.0M
Howard Hughes Medical Institute InvestigatorNIAID NIH HHS 75N93021C00015NIAID NIH HHS HHSN272201400006CNIAID NIH HHS HHSN272201400006C,NIAID NIH HHS R01 AI141707NIAID NIH HHS R01AI1417097NIGMS NIH HHS R35 GM142886NIGMS NIH HHS R35GM142886
6 · The paper itself

Abstract

Neutralization assays are experimental surrogates for the effectiveness of infection- or vaccine-elicited polyclonal antibodies and therapeutic monoclonal antibodies targeting SARS-CoV-2. However, the measured neutralization can depend on the details of the experimental assay. Here, we systematically assess how ACE2 expression in target cells affects neutralization by antibodies to different spike epitopes in lentivirus pseudovirus neutralization assays. For high ACE2-expressing target cells, receptor-binding domain (RBD) antibodies account for nearly all neutralizing activity in polyclonal human sera. However, for lower ACE2-expressing target cells, antibodies targeting regions outside the RBD make a larger (although still modest) contribution to serum neutralization. These serum-level results are mirrored for monoclonal antibodies: N-terminal domain (NTD) antibodies and RBD antibodies that do not compete for ACE2 binding incompletely neutralize on high ACE2-expressing target cells, but completely neutralize on cells with lower ACE2 expression. Our results show that the ACE2 expression level in the target cells is an important experimental variable, and that high ACE2 expression emphasizes the role of a subset of RBD-directed antibodies.

Indexed as

COVID-19SARS-CoV-2Angiotensin-Converting Enzyme 2Antibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralEpitopesHumansSpike Glycoprotein, CoronavirusAngiotensin-Converting Enzyme 2Antibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralEpitopesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2ACE2neutralization assayneutralizing antibody epitopesNTDpseudovirusRBDSARS-CoV-2target cell receptor expression

Identifiers

PMID36146867
PMCPMC9504593
OpenAlexW4296809648

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.