Evidence map›Paper›PMID 35347138›Full record

ArticleNature communications2022

Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617.

Lei Peng, Yingxia Hu, Madeleine C Mankowski, Ping Ren, Rita E Chen, Jin Wei, Min Zhao, Tongqing Li, Therese Tripler, Lupeng Ye and 14 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.0field-weighted citation impact, top 12% 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

13 citing papers in PubMed, 21 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 3 institutions in 1 country.

Lei Peng *Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Yingxia Hu *Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
Madeleine C Mankowski *Department of Laboratory Medicine, Yale University, New Haven, CT, USA.
Ping Ren *Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Rita E ChenDepartments of Medicine and Pathology & Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
Jin WeiDepartment of Laboratory Medicine, Yale University, New Haven, CT, USA.
Min ZhaoSection of Infectious Diseases, Department of Internal Medicine, Yale University, New Haven, CT, USA.
Tongqing LiDepartment of Pharmacology, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-5272-4380
Therese TriplerDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
Lupeng YeDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-3901-6598
Ryan D ChowDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-1872-6307
Zhenhao FangDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Chunxiang WuDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-8635-1578
Matthew B DongDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Matthew CookDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
Guilin WangYale Center for Genome Analysis, Yale University, New Haven, CT, USA.
Paul ClarkDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Bryce NelsonDepartment of Pharmacology, Yale University School of Medicine, New Haven, CT, USA.
Daryl KleinDepartment of Pharmacology, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-7188-0450
Richard SuttonSection of Infectious Diseases, Department of Internal Medicine, Yale University, New Haven, CT, USA.
Michael S DiamondDepartments of Medicine and Pathology & Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-8791-3165
Craig B WilenDepartment of Laboratory Medicine, Yale University, New Haven, CT, USA. craig.wilen@yale.edu.ORCID http://orcid.org/0000-0003-2495-9403
Yong XiongDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA. yong.xiong@yale.edu.ORCID http://orcid.org/0000-0001-9625-9313
Sidi ChenDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA. sidi.chen@yale.edu.ORCID http://orcid.org/0000-0002-3819-5005
Yale University · USYale Cancer Center · USWashington University in St. Louis · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
NATIONAL RESEARCH SERVICE AWARD-MEDICAL SCIENTISTT32GM007200 · NIGMS · WASHINGTON UNIVERSITY · PI YOKOYAMA, WAYNE M. · 1985 to 2024
$59.8M
INTERDISCIPLINARY IMMUNOLOGY TRAINING PROGRAMT32AI007019 · NIAID · YALE UNIVERSITY · PI Carrie L. Lucas, David G. Schatz · 1985 to 2026
$14.4M
Human antibody-based countermeasures against the Wuhan Coronavirus SARS-CoV-2R01AI157155 · NIAID · WASHINGTON UNIVERSITY · PI BARIC, RALPH S, CROWE, JAMES E · 2020 to 2024
$6.0M
Structure and Dynamics of the SARS-CoV-2 Spike ProteinR01AI163395 · NIAID · YALE UNIVERSITY · PI MOTHES, WALTHER H · 2021 to 2025
$4.1M
The role of tuft cells in norovirus pathogenesisR01AI148467 · NIAID · YALE UNIVERSITY · PI Craig Brian Wilen · 2020 to 2026
$3.9M
Mechanisms of transcriptional regulation of ccr5 and host genetic control of HIVR01AI150334 · NIAID · YALE UNIVERSITY · PI SUTTON, RICHARD · 2020 to 2024
$3.5M
Role of virus-receptor interactions in determining norovirus tropism and pathogenesis in vivoK08AI128043 · NIAID · YALE UNIVERSITY · PI WILEN, CRAIG BRIAN · 2017 to 2021
$940k
High Performance Computing Instrumentation for the Yale Center for Genome AnalysiS10OD018521 · OD · YALE UNIVERSITY · PI MANE, SHRIKANT M · 2015 to 2015
$890k
Biacore T100 SPR system for studying and characterizing biomolecular interactionS10RR026992 · NCRR · YALE UNIVERSITY · PI FOLTA-STOGNIEW, EWA JOANNA · 2009 to 2009
$364k
NCATS NIH HHS UL1 TR001863NCRR NIH HHS S10RR026992-0110NIAID NIH HHS K08 AI128043NIAID NIH HHS R01 AI148467NIAID NIH HHS R01 AI150334NIAID NIH HHS R01 AI157155NIAID NIH HHS R01 AI163395NIAID NIH HHS T32 AI007019NIGMS NIH HHS T32 GM007200NIH HHS 1S10OD018521NIH HHS S10 OD018521U.S. Department of Defense (United States Department of Defense) W81XWH-21-1-0019
6 · The paper itself

Abstract

COVID-19 pathogen SARS-CoV-2 has infected hundreds of millions and caused over 5 million deaths to date. Although multiple vaccines are available, breakthrough infections occur especially by emerging variants. Effective therapeutic options such as monoclonal antibodies (mAbs) are still critical. Here, we report the development, cryo-EM structures, and functional analyses of mAbs that potently neutralize SARS-CoV-2 variants of concern. By high-throughput single cell sequencing of B cells from spike receptor binding domain (RBD) immunized animals, we identify two highly potent SARS-CoV-2 neutralizing mAb clones that have single-digit nanomolar affinity and low-picomolar avidity, and generate a bispecific antibody. Lead antibodies show strong inhibitory activity against historical SARS-CoV-2 and several emerging variants of concern. We solve several cryo-EM structures at ~3 Å resolution of these neutralizing antibodies in complex with prefusion spike trimer ectodomain, and reveal distinct epitopes, binding patterns, and conformations. The lead clones also show potent efficacy in vivo against authentic SARS-CoV-2 in both prophylactic and therapeutic settings. We also generate and characterize a humanized antibody to facilitate translation and drug development. The humanized clone also has strong potency against both the original virus and the B.1.617.2 Delta variant. These mAbs expand the repertoire of therapeutics against SARS-CoV-2 and emerging variants.

Indexed as

Antibodies, NeutralizingAntibodies, ViralCOVID-19SARS-CoV-2AnimalsAntibodies, BispecificAntibodies, Monoclonal, HumanizedSpike Glycoprotein, CoronavirusViral Envelope ProteinsAntibodies, BispecificAntibodies, Monoclonal, HumanizedAntibodies, NeutralizingAntibodies, ViralSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Viral Envelope Proteins

Identifiers

PMID35347138
PMCPMC8960874
OpenAlexW4220820269

What OpenQuestion holds

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LicenceCC BY
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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.