Evidence map›Paper›PMID 29462889›Full record

ArticleToxins2018

A Single Tri-Epitopic Antibody Virtually Recapitulates the Potency of a Combination of Three Monoclonal Antibodies in Neutralization of Botulinum Neurotoxin Serotype A.

Jianlong Lou, Weihua Wen, Fraser Conrad, Qi Meng, Jianbo Dong, Zhengda Sun, Consuelo Garcia-Rodriguez, Shauna Farr-Jones, Luisa W Cheng, Thomas D Henderson and 5 more

Abstract read
In one paragraph

Article in Toxins, 2018. 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
–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

8 citing papers in PubMed.

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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.

Jianlong LouDepartment of Anesthesia and Perioperative Care, University of California, San Francisco Rm 3C-38, San Francisco General Hospital, 1001 Potrero Ave, San Francisco, CA 94110, USA. jianlong.lou@ucsf.edu.
Weihua WenDepartment of Anesthesia and Perioperative Care, University of California, San Francisco Rm 3C-38, San Francisco General Hospital, 1001 Potrero Ave, San Francisco, CA 94110, USA. weihua.wen@ucsf.edu.
Fraser ConradDepartment of Anesthesia and Perioperative Care, University of California, San Francisco Rm 3C-38, San Francisco General Hospital, 1001 Potrero Ave, San Francisco, CA 94110, USA. fraser.conrad@ucsf.edu.ORCID 0000-0001-6908-8475
Qi MengDepartment of Anesthesia and Perioperative Care, University of California, San Francisco Rm 3C-38, San Francisco General Hospital, 1001 Potrero Ave, San Francisco, CA 94110, USA. fanqimeng@gmail.com.
Jianbo DongDepartment of Anesthesia and Perioperative Care, University of California, San Francisco Rm 3C-38, San Francisco General Hospital, 1001 Potrero Ave, San Francisco, CA 94110, USA. jianbodong@gmail.com.
Zhengda SunDepartment of Anesthesia and Perioperative Care, University of California, San Francisco Rm 3C-38, San Francisco General Hospital, 1001 Potrero Ave, San Francisco, CA 94110, USA. zhengda.sun@ucsf.edu.
Consuelo Garcia-RodriguezDepartment of Anesthesia and Perioperative Care, University of California, San Francisco Rm 3C-38, San Francisco General Hospital, 1001 Potrero Ave, San Francisco, CA 94110, USA. MariaConsuelo.Garcia@ucsf.edu.
Shauna Farr-JonesDepartment of Anesthesia and Perioperative Care, University of California, San Francisco Rm 3C-38, San Francisco General Hospital, 1001 Potrero Ave, San Francisco, CA 94110, USA. Shauna.farr-jones@ucsf.edu.ORCID 0000-0003-4130-6332
Luisa W ChengWestern Regional Research Center, Agricultural Research Service, United States Department of Agriculture, Albany, CA 94710, USA. luisa.cheng@ars.usda.gov.
Thomas D HendersonWestern Regional Research Center, Agricultural Research Service, United States Department of Agriculture, Albany, CA 94710, USA. Thomas.henderson@ars.usda.gov.
Jennifer L BrownMolecular and Translational Sciences Division, United States Army Medical Institute of Infectious Disease, Fort Detrick, MD 21702, USA. jennifer.l.brown436.ctr@mail.mil.
Theresa J SmithMolecular and Translational Sciences Division, United States Army Medical Institute of Infectious Disease, Fort Detrick, MD 21702, USA. terrys2much@comcast.net.
Leonard A SmithU. S. Army Medical Research and Materiel Command, Fort Detrick, MD 21702, USA. leonard.a.smith@comcast.net.
Anthony CormierDepartment of Pathology, University of California, San Francisco, ZSFG/UCSF, Bldg 3/ Rm 211, 1001 Potrero Ave., San Francisco, CA 94158, USA. Anthony.Cormier@ucsf.edu.ORCID 0000-0002-2848-9536
James D MarksDepartment of Anesthesia and Perioperative Care, University of California, San Francisco Rm 3C-38, San Francisco General Hospital, 1001 Potrero Ave, San Francisco, CA 94110, USA. Jim.Marks@ucsf.edu.

Funding

Development of botulinum neurotoxin immunotherapyU01AI056493 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARKS, JAMES D. · 2003 to 2007
$5.1M
Trispecific monoclonal antibody for botulinum neurotoxin intoxication therapyR33AI101539 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARKS, JAMES D. · 2014 to 2016
$1.3M
Trispecific monoclonal antibody for botulinum neurotoxin intoxication therapyR21AI101539 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARKS, JAMES D. · 2012 to 2013
$409k
NIAID NIH HHS R21 AI101539NIAID NIH HHS R33 AI101539NIAID NIH HHS U01 AI056493
6 · The paper itself

Abstract

The standard of treatment for botulism, equine antitoxin, is a foreign protein with associated safety issues and a short serum half-life which excludes its use as a prophylactic antitoxin and makes it a less-than-optimal therapeutic. Due to these limitations, a recombinant monoclonal antibody (mAb) product is preferable. It has been shown that combining three mAbs that bind non-overlapping epitopes leads to highly potent botulinum neurotoxin (BoNT) neutralization. Recently, a triple human antibody combination for BoNT/A has demonstrated potent toxin neutralization in mouse models with no serious adverse events when tested in a Phase I clinical trial. However, a triple antibody therapeutic poses unique development and manufacturing challenges. Thus, potentially to streamline development of BoNT antitoxins, we sought to achieve the potency of multiple mAb combinations in a single IgG-based molecule that has a long serum half-life. The design, production, and testing of a single tri-epitopic IgG1-based mAb (TeAb) containing the binding sites of each of the three parental BoNT/A mAbs yielded an antibody of nearly equal potency to the combination. The approach taken here could be applied to the design and creation of other multivalent antibodies that could be used for a variety of applications, including toxin elimination.

Indexed as

AnimalsAntibodies, MonoclonalBotulinum Toxins, Type ACHO CellsCricetulusEpitopesFemaleMiceNeuronsNeutralization TestsRatsAntibodies, MonoclonalBotulinum Toxins, Type AEpitopesantitoxinbi-epitopicbotulinum neurotoxinbotulismkinetic-exclusion analysismouse neutralization assaymultivalent antibodynegative-stain electron microscopyrecombinant monoclonal antibodytri-epitopic

Identifiers

PMID29462889
PMCPMC5848185

What OpenQuestion holds

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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.