ArticlePloS one2015
Monoclonal Antibodies Targeting the Alpha-Exosite of Botulinum Neurotoxin Serotype/A Inhibit Catalytic Activity.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Nanoyeast-based impedimetric biosensor with mutated single chain antigen-binding fragment anchoring for SARS-CoV-2 detection.Biomedical microdevices · 2026Article
- Recombinant expression of receptor binding domains of all eight subtypes of botulinum neurotoxin type A for generation of antitoxins with broad reactivity.F1000Research · 2025Article
- Development of Effective Medical Countermeasures Against the Main Biowarfare Agents: The Importance of Antibodies.Microorganisms · 2024Review
- Regulation of Peptidase Activity beyond the Active Site in Human Health and Disease.International journal of molecular sciences · 2023Review
- Article
- Probing the structure and function of the protease domain of botulinum neurotoxins using single-domain antibodies.PLoS pathogens · 2022Article
- Multicolor fluorescence activated cell sorting to generate humanized monoclonal antibody binding seven subtypes of BoNT/F.PloS one · 2022Article
- A Four-Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotypes C and D.Toxins · 2021Article
- Activity-dependent somatodendritic dopamine release in the substantia nigra autoinhibits the releasing neuron.Cell reports · 2021Article
- The Novel Clostridial Neurotoxin Produced by Strain IBCA10-7060 Is Immunologically Equivalent to BoNT/HA.Toxins · 2019Article
- Antibodies and Vaccines against Botulinum Toxins: Available Measures and Novel Approaches.Toxins · 2019Review
- A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes.Toxins · 2018Article
- Article
- A three monoclonal antibody combination potently neutralizes multiple botulinum neurotoxin serotype F subtypes.PloS one · 2017Article
- Picolinic acids as β-exosite inhibitors of botulinum neurotoxin A light chain.Chemical communications (Cambridge, England) · 2016Article
- Use of Monoclonal Antibodies in the Sensitive Detection and Neutralization of Botulinum Neurotoxin Serotype B.Toxins · 2015Article
- Monoclonal Antibodies that Inhibit the Proteolytic Activity of Botulinum Neurotoxin Serotype/B.Toxins · 2015Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
The paralytic disease botulism is caused by botulinum neurotoxins (BoNT), multi-domain proteins containing a zinc endopeptidase that cleaves the cognate SNARE protein, thereby blocking acetylcholine neurotransmitter release. Antitoxins currently used to treat botulism neutralize circulating BoNT but cannot enter, bind to or neutralize BoNT that has already entered the neuron. The light chain endopeptidase domain (LC) of BoNT serotype A (BoNT/A) was targeted for generation of monoclonal antibodies (mAbs) that could reverse paralysis resulting from intoxication by BoNT/A. Single-chain variable fragment (scFv) libraries from immunized humans and mice were displayed on the surface of yeast, and 19 BoNT/A LC-specific mAbs were isolated by using fluorescence-activated cell sorting (FACS). Affinities of the mAbs for BoNT/A LC ranged from a KD value of 9.0×10-11 M to 3.53×10-8 M (mean KD 5.38×10-9 M and median KD 1.53×10-9 M), as determined by flow cytometry analysis. Eleven mAbs inhibited BoNT/A LC catalytic activity with IC50 values ranging from 8.3 ~73×10-9 M. The fine epitopes of selected mAbs were also mapped by alanine-scanning mutagenesis, revealing that the inhibitory mAbs bound the α-exosite region remote from the BoNT/A LC catalytic center. The results provide mAbs that could prove useful for intracellular reversal of paralysis post-intoxication and further define epitopes that could be targeted by small molecule inhibitors.
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Registered trials
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.