Evidence map›Paper›PMID 33666135›Full record

ArticlemAbs

Bispecific VH/Fab antibodies targeting neutralizing and non-neutralizing Spike epitopes demonstrate enhanced potency against SARS-CoV-2.

Shion A Lim, Josef A Gramespacher, Katarina Pance, Nicholas J Rettko, Paige Solomon, Jing Jin, Irene Lui, Susanna K Elledge, Jia Liu, Colton J Bracken and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
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 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.0field-weighted citation impact, top 11% 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

24 citing papers in PubMed, 35 citations in OpenAlex.

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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

14 authors at 2 institutions in 1 country.

Shion A LimDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, USA.
Josef A GramespacherDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, USA.
Katarina PanceDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, USA.
Nicholas J RettkoDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, USA.
Paige SolomonDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, USA.
Jing JinVitalant Research Institute and Department of Laboratory Medicine, University of California San Francisco, University of California San Francisco, California, USA.
Irene LuiDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, USA.
Susanna K ElledgeDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, USA.
Jia LiuDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, USA.
Colton J BrackenDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, USA.
Graham SimmonsVitalant Research Institute and Department of Laboratory Medicine, University of California San Francisco, University of California San Francisco, California, USA.
Xin X ZhouDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, USA.
Kevin K LeungDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, USA.
James A WellsDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, USA.
University of California, San Francisco · USVitalant · US

Funding

Surfaceomic technologies and antibodies to probe cell surface proteomes and their interactomes at unprecedented small scale and high-resolutionR35GM122451 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JAMES A WELLS · 2017 to 2026
$5.3M
NIGMS NIH HHS R35 GM122451NIGMS NIH HHS R35 GM122451-01
6 · The paper itself

Abstract

Numerous neutralizing antibodies that target SARS-CoV-2 have been reported, and most directly block binding of the viral Spike receptor-binding domain (RBD) to angiotensin-converting enzyme II (ACE2). Here, we deliberately exploit non-neutralizing RBD antibodies, showing they can dramatically assist in neutralization when linked to neutralizing binders. We identified antigen-binding fragments (Fabs) by phage display that bind RBD, but do not block ACE2 or neutralize virus as IgGs. When these non-neutralizing Fabs were assembled into bispecific VH/Fab IgGs with a neutralizing VH domain, we observed a ~ 25-fold potency improvement in neutralizing SARS-CoV-2 compared to the mono-specific bi-valent VH-Fc alone or the cocktail of the VH-Fc and IgG. This effect was epitope-dependent, reflecting the unique geometry of the bispecific antibody toward Spike. Our results show that a bispecific antibody that combines both neutralizing and non-neutralizing epitopes on Spike-RBD is a promising and rapid engineering strategy to improve the potency of SARS-CoV-2 antibodies.

Indexed as

Antibodies, BispecificAntibodies, NeutralizingAntibodies, ViralCOVID-19COVID-19 Drug TreatmentEpitopesHEK293 CellsHumansImmunoglobulin Fab FragmentsSARS-CoV-2Spike Glycoprotein, CoronavirusAntibodies, BispecificAntibodies, NeutralizingAntibodies, ViralEpitopesImmunoglobulin Fab FragmentsSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2BispecificCOVID-19knob-in-holeneutralizing antibodySARS-CoV-2

Identifiers

PMID33666135
PMCPMC7939556
OpenAlexW3133886945

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.