Evidence map›Paper›PMID 34564645›Full record

ArticleToxins2021

A Four-Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotypes C and D.

Consuelo Garcia-Rodriguez, Shude Yan, Isin N Geren, Kristeene A Knopp, Jianbo Dong, Zhengda Sun, Jianlong Lou, Fraser Conrad, Wei-Hua Wen, Shauna Farr-Jones and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Toxins, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.8field-weighted citation impact, top 25% 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

10 citing papers in PubMed, 10 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

15 authors at 2 institutions in 1 country.

Consuelo Garcia-RodriguezDepartment of Anesthesia & Perioperative Care, University of California, San Francisco, Zuckerberg San Francisco General Hospital and Trauma Center, 1001 Potrero Avenue, San Francisco, CA 94110, USA.
Shude YanDepartment of Anesthesia & Perioperative Care, University of California, San Francisco, Zuckerberg San Francisco General Hospital and Trauma Center, 1001 Potrero Avenue, San Francisco, CA 94110, USA.
Isin N GerenDepartment of Anesthesia & Perioperative Care, University of California, San Francisco, Zuckerberg San Francisco General Hospital and Trauma Center, 1001 Potrero Avenue, San Francisco, CA 94110, USA.
Kristeene A KnoppDepartment of Anesthesia & Perioperative Care, University of California, San Francisco, Zuckerberg San Francisco General Hospital and Trauma Center, 1001 Potrero Avenue, San Francisco, CA 94110, USA.
Jianbo DongDepartment of Anesthesia & Perioperative Care, University of California, San Francisco, Zuckerberg San Francisco General Hospital and Trauma Center, 1001 Potrero Avenue, San Francisco, CA 94110, USA.
Zhengda SunDepartment of Anesthesia & Perioperative Care, University of California, San Francisco, Zuckerberg San Francisco General Hospital and Trauma Center, 1001 Potrero Avenue, San Francisco, CA 94110, USA.
Jianlong LouDepartment of Anesthesia & Perioperative Care, University of California, San Francisco, Zuckerberg San Francisco General Hospital and Trauma Center, 1001 Potrero Avenue, San Francisco, CA 94110, USA.
Fraser ConradDepartment of Anesthesia & Perioperative Care, University of California, San Francisco, Zuckerberg San Francisco General Hospital and Trauma Center, 1001 Potrero Avenue, San Francisco, CA 94110, USA.ORCID 0000-0001-6908-8475
Wei-Hua WenDepartment of Anesthesia & Perioperative Care, University of California, San Francisco, Zuckerberg San Francisco General Hospital and Trauma Center, 1001 Potrero Avenue, San Francisco, CA 94110, USA.
Shauna Farr-JonesDepartment of Anesthesia & Perioperative Care, University of California, San Francisco, Zuckerberg San Francisco General Hospital and Trauma Center, 1001 Potrero Avenue, San Francisco, CA 94110, USA.ORCID 0000-0003-4130-6332
Theresa J SmithMolecular and Translational Sciences Division, United States Army Medical Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USA.
Jennifer L BrownKe'aki Technologies LLC, United States Army Medical Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USA.
Janet C SkerryKe'aki Technologies LLC, United States Army Medical Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USA.
Leonard A SmithMedical Countermeasures Technology, United States Army Medical Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USA.
James D MarksDepartment of Anesthesia & Perioperative Care, University of California, San Francisco, Zuckerberg San Francisco General Hospital and Trauma Center, 1001 Potrero Avenue, San Francisco, CA 94110, USA.ORCID 0000-0003-0562-3517
San Francisco General Hospital · USUnited States Army Medical Research Institute of Infectious Diseases · US

Funding

Development of botulinum neurotoxin immunotherapyU01AI056493 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARKS, JAMES D. · 2003 to 2007
$5.1M
NIAID NIH HHS U01 AI056493
6 · The paper itself

Abstract

Human botulism can be caused by botulinum neurotoxin (BoNT) serotypes A to G. Here, we present an antibody-based antitoxin composed of four human monoclonal antibodies (mAbs) against BoNT/C, BoNT/D, and their mosaic toxins. This work built on our success in generating protective mAbs to BoNT /A, B and E serotypes. We generated mAbs from human immune single-chain Fv (scFv) yeast-display libraries and isolated scFvs with high affinity for BoNT/C, BoNT/CD, BoNT/DC and BoNT/D serotypes. We identified four mAbs that bound non-overlapping epitopes on multiple serotypes and mosaic BoNTs. Three of the mAbs underwent molecular evolution to increase affinity. A four-mAb combination provided high-affinity binding and BoNT neutralization of both serotypes and their mosaic toxins. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing and neutralizing BoNT/C and BoNT/D serotypes and their mosaic toxins. A derivative of the four-antibody combination (NTM-1634) completed a Phase 1 clinical trial (Snow et al., Antimicrobial Agents and Chemotherapy, 2019) with no drug-related serious adverse events.

Indexed as

AnimalsAntibodies, MonoclonalBotulinum ToxinsBotulismFemaleHumansMiceSerogroupAntibodies, MonoclonalBotulinum Toxinsbotulinum toxin type Cbotulinum toxin type Dantibody engineeringbotulinum antitoxinbotulinum neurotoxinmouse neutralization assayoligoclonal antibodiesrecombinant antibodiesserotype C botulismserotype D botulism

Identifiers

PMID34564645
PMCPMC8472335
OpenAlexW3201336064

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.