Evidence map›Paper›PMID 37063468›Full record

ArticleiScience2023

Bispecific antibodies combine breadth, potency, and avidity of parental antibodies to neutralize sarbecoviruses.

Laura Radić, Kwinten Sliepen, Victor Yin, Mitch Brinkkemper, Joan Capella-Pujol, Angela I Schriek, Jonathan L Torres, Sandhya Bangaru, Judith A Burger, Meliawati Poniman and 9 more

Open access · goldAbstract read
In one paragraph

Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

8 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Bispecific antibodies against the hepatitis C virus E1E2 envelope glycoprotein.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  3. Article
  4. Article
  5. Oligomerization-driven avidity correlates with SARS-CoV-2 cellular binding and inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  6. Article
  7. Article
  8. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 5 institutions in 2 countries.

Laura RadićAmsterdam UMC location University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
Kwinten SliepenAmsterdam UMC location University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
Victor YinBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CH Utrecht, the Netherlands.
Mitch BrinkkemperAmsterdam UMC location University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
Joan Capella-PujolAmsterdam UMC location University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
Angela I SchriekAmsterdam UMC location University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
Jonathan L TorresDepartment of Structural Biology and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Sandhya BangaruDepartment of Structural Biology and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Judith A BurgerAmsterdam UMC location University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
Meliawati PonimanAmsterdam UMC location University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
Ilja BontjerAmsterdam UMC location University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
Joey H BouhuijsAmsterdam UMC location University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
David GideonseCenter for Infectious Disease Control, WHO COVID-19 reference laboratory, National Institute for Public Health and the Environment (RIVM), 3721 MA Bilthoven, the Netherlands.
Dirk EgginkCenter for Infectious Disease Control, WHO COVID-19 reference laboratory, National Institute for Public Health and the Environment (RIVM), 3721 MA Bilthoven, the Netherlands.
Andrew B WardDepartment of Structural Biology and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Albert J R HeckBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CH Utrecht, the Netherlands.
Marit J Van GilsAmsterdam UMC location University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
Rogier W SandersAmsterdam UMC location University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
Janke SchinkelAmsterdam UMC location University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
Amsterdam University Medical Centers · NLUniversity of Amsterdam · NLScripps Research Institute · USNational Institute for Public Health and the Environment · NLNetherlands Metabolomics Centre · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

SARS-CoV-2 variants evade current monoclonal antibody therapies. Bispecific antibodies (bsAbs) combine the specificities of two distinct antibodies taking advantage of the avidity and synergy provided by targeting different epitopes. Here we used controlled Fab-arm exchange to produce bsAbs that neutralize SARS-CoV and SARS-CoV-2 variants, including Omicron and its subvariants, by combining potent SARS-CoV-2-specific neutralizing antibodies with broader antibodies that also neutralize SARS-CoV. We demonstrated that the parental antibodies rely on avidity for neutralization using bsAbs containing one irrelevant Fab arm. Using mass photometry to measure the formation of antibody:spike complexes, we determined that bsAbs increase binding stoichiometry compared to corresponding cocktails, without a loss of binding affinity. The heterogeneous binding pattern of bsAbs to spike, observed by negative-stain electron microscopy and mass photometry provided evidence for both intra- and inter-spike crosslinking. This study highlights the utility of cross-neutralizing antibodies for designing bivalent agents to combat circulating and future SARS-like coronaviruses.

Indexed as

ImmunologyStructural biologyVirology

Identifiers

PMID37063468
PMCPMC10065043
OpenAlexW4362474630

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.