Evidence map›Paper›PMID 35293276›Full record

ArticlemAbs

Comprehensive engineering of a therapeutic neutralizing antibody targeting SARS-CoV-2 spike protein to neutralize escape variants.

Taichi Kuramochi, Siok Wan Gan, Adrian W S Ho, Bei Wang, Nagisa Kageji, Takeru Nambu, Sayaka Iida, Momoko Okuda-Miura, Wei Shan Chia, Chiew Ying Yeo and 7 more

Abstract read
In one paragraph

Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Positive-strand RNA viruses-a Keystone Symposia report.Annals of the New York Academy of Sciences · 2023
    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

17 authors.

Taichi KuramochiDiscovery Biologics Department, Research Division, Chugai Pharmaceutical Co., Ltd., Kamakura, Kanagawa, Japan.ORCID 0000-0001-7242-7124
Siok Wan GanProtein Analysis Unit, Research Division, Chugai Pharmabody Research Pte. Ltd, Singapore.
Adrian W S HoProtein Analysis Unit, Research Division, Chugai Pharmabody Research Pte. Ltd, Singapore.
Bei WangPharmacology Unit, Research Division, Chugai Pharmabody Research Pte. Ltd, Singapore.ORCID 0000-0002-3112-7341
Nagisa Kageji
Takeru NambuProtein Analysis Unit, Research Division, Chugai Pharmabody Research Pte. Ltd, Singapore.
Sayaka IidaProtein Analysis Unit, Research Division, Chugai Pharmabody Research Pte. Ltd, Singapore.
Momoko Okuda-MiuraProtein Analysis Unit, Research Division, Chugai Pharmabody Research Pte. Ltd, Singapore.
Wei Shan ChiaProtein Analysis Unit, Research Division, Chugai Pharmabody Research Pte. Ltd, Singapore.
Chiew Ying YeoProtein Analysis Unit, Research Division, Chugai Pharmabody Research Pte. Ltd, Singapore.
Dan ChenProtein Analysis Unit, Research Division, Chugai Pharmabody Research Pte. Ltd, Singapore.ORCID 0000-0002-2790-5606
Wen-Hsin LeePharmacology Unit, Research Division, Chugai Pharmabody Research Pte. Ltd, Singapore.ORCID 0000-0003-0315-7495
Eve Zi Xian NgohPharmacology Unit, Research Division, Chugai Pharmabody Research Pte. Ltd, Singapore.ORCID 0000-0001-5407-0280
Siti Nazihah Mohd SallehPharmacology Unit, Research Division, Chugai Pharmabody Research Pte. Ltd, Singapore.
Cheng-I WangPharmacology Unit, Research Division, Chugai Pharmabody Research Pte. Ltd, Singapore.ORCID 0000-0001-9170-2996
Tomoyuki IgawaDiscovery Pharmacology Department, Research Division, Chugai Pharmaceutical Co. Ltd ., Kamakura, Kanagawa, Japan.
Hideaki ShimadaProtein Analysis Unit, Research Division, Chugai Pharmabody Research Pte. Ltd, Singapore.ORCID 0000-0003-4932-1385

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The emergence of escape variants of SARS-CoV-2 carrying mutations in the spike protein poses a challenge for therapeutic antibodies. Here, we show that through the comprehensive engineering of the variable region of the neutralizing monoclonal antibody 5A6, the engineered antibody, 5A6CCS1, is able to neutralize SARS-CoV-2 variants that escaped neutralization by the original 5A6 antibody. In addition to the improved affinity against variants, 5A6CCS1 was also optimized to achieve high solubility and low viscosity, enabling a high concentration formulation for subcutaneous injection. In cynomolgus monkeys, 5A6CCS1 showed a long plasma half-life and good subcutaneous bioavailability through engineering of the variable and constant region. These data demonstrate that 5A6CCS1 is a promising antibody for development against SARS-CoV-2 and highlight the importance of antibody engineering as a potential method to counteract escape variants.

Indexed as

COVID-19Spike Glycoprotein, CoronavirusAntibodies, NeutralizingAntibodies, ViralHumansMembrane GlycoproteinsNeutralization TestsSARS-CoV-2Viral Envelope ProteinsAntibodies, NeutralizingAntibodies, ViralMembrane GlycoproteinsSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Viral Envelope Proteinsantibody engineeringescape variantsSARS-CoV-2Therapeutic antibody

Identifiers

PMID35293276
PMCPMC8932922

What OpenQuestion holds

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LicenceCC BY-NC
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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.