Evidence map›Paper›PMID 34006961›Full record

ArticleScientific reports2021

Implementing a method for engineering multivalency to substantially enhance binding of clinical trial anti-SARS-CoV-2 antibodies to wildtype spike and variants of concern proteins.

Adam Leach, Ami Miller, Emma Bentley, Giada Mattiuzzo, Jemima Thomas, Craig McAndrew, Rob Van Montfort, Terence Rabbitts

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.7field-weighted citation impact, top 28% 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

4 citing papers in PubMed, 11 citations in OpenAlex.

  1. 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
  2. Article
  3. Review
  4. 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

8 authors at 2 institutions in 1 country.

Adam Leach *Institute of Cancer Research, 15 Cotswold Road, Sutton, London, SM2 5NG, UK.
Ami Miller *Institute of Cancer Research, 15 Cotswold Road, Sutton, London, SM2 5NG, UK.
Emma BentleyNational Institute for Biological Standards and Control, Blanche Lane, South Mimms, Hertfordshire, EN6 3QG, UK.
Giada MattiuzzoNational Institute for Biological Standards and Control, Blanche Lane, South Mimms, Hertfordshire, EN6 3QG, UK.
Jemima ThomasInstitute of Cancer Research, 15 Cotswold Road, Sutton, London, SM2 5NG, UK.
Craig McAndrewInstitute of Cancer Research, 15 Cotswold Road, Sutton, London, SM2 5NG, UK.
Rob Van MontfortInstitute of Cancer Research, 15 Cotswold Road, Sutton, London, SM2 5NG, UK.
Terence RabbittsInstitute of Cancer Research, 15 Cotswold Road, Sutton, London, SM2 5NG, UK. terry.rabbitts@icr.ac.uk.
Institute of Cancer Research · GBNational Institute for Biological Standards and Control · GB

Funding

Blood Cancer UK 19013Cancer Research UK 19013Cancer Research UK C2739/A2289
6 · The paper itself

Abstract

Infection by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes COVID-19 disease. Therapeutic antibodies are being developed that interact with the viral spike proteins to limit viral infection of epithelium. We have applied a method to dramatically improve the performance of anti-SARS-CoV-2 antibodies by enhancing avidity through multimerization using simple engineering to yield tetrameric antibodies. We have re-engineered six anti-SARS-CoV-2 antibodies using the human p53 tetramerization domain, including three clinical trials antibodies casirivimab, imdevimab and etesevimab. The method yields tetrameric antibodies, termed quads, that retain efficient binding to the SARS-CoV-2 spike protein, show up to two orders of magnitude enhancement in neutralization of pseudovirus infection and retain potent interaction with virus variant of concern spike proteins. The tetramerization method is simple, general and its application is a powerful methodological development for SARS-CoV-2 antibodies that are currently in pre-clinical and clinical investigation.

Indexed as

Antibodies, NeutralizingAntigen-Antibody ReactionsCOVID-19COVID-19 Drug TreatmentEnzyme-Linked Immunosorbent AssayHEK293 CellsHumansNeutralization TestsProtein DomainsProtein MultimerizationRecombinant ProteinsSARS-CoV-2Single-Chain AntibodiesSpike Glycoprotein, CoronavirusSurface Plasmon ResonanceTumor Suppressor Protein p53Antibodies, NeutralizingRecombinant ProteinsSingle-Chain AntibodiesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2TP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID34006961
PMCPMC8131632
OpenAlexW3163551129

What OpenQuestion 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 OpenQuestion graph.