ArticlePloS one2015
Development of Human-Like scFv-Fc Neutralizing Botulinum Neurotoxin E.
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 14 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
14 citing papers in PubMed, 23 citations in OpenAlex.
- Neutralizing anti-diphtheria toxin scFv produced by phage display.Biotechnology letters · 2024Article
- A human bispecific antibody neutralizes botulinum neurotoxin serotype A.Scientific reports · 2023Article
- Antibody Selection in Solution Using Magnetic Beads.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Functional EL-HN Fragment as a Potent Candidate Vaccine for the Prevention of Botulinum Neurotoxin Serotype E.Toxins · 2022Article
- Developing Recombinant Antibodies by Phage Display Against Infectious Diseases and Toxins for Diagnostics and Therapy.Frontiers in cellular and infection microbiology · 2021Review
- Article
- The European AntibotABE Framework Program and Its Update: Development of Innovative Botulinum Antibodies.Toxins · 2017Review
- Designing Human Antibodies by Phage Display.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2017Review
- Role of Homologous Fc Fragment in the Potency and Efficacy of Anti-Botulinum Antibody Preparations.Toxins · 2017Article
- Recombinant antibodies for diagnostics and therapy against pathogens and toxins generated by phage display.Proteomics. Clinical applications · 2016Review
- Review
- Article
- Tetanus Neurotoxin Neutralizing Antibodies Screened from a Human Immune scFv Antibody Phage Display Library.Toxins · 2016Article
- Development of Germline-Humanized Antibodies Neutralizing Botulinum Neurotoxin A and B.PloS one · 2016Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
Abstract
backgroundBotulinum neurotoxins (BoNTs) are considered to be the most toxic substances known on earth and are responsible for human botulism, a life-threatening disease characterized by flaccid muscle paralysis that occurs naturally by food-poisoning or colonization of the gastrointestinal tract by BoNT-producing clostridia. BoNTs have been classified as category A agent by the Centers of Disease Control and Prevention (CDC) and are listed among the six agents with the highest risk to be used as bioweapons. Neutralizing antibodies are required for the development of effective anti-botulism therapies to deal with the potential risk of exposure.
resultsIn this study, a macaque (Macaca fascicularis) was immunized with recombinant light chain of BoNT/E3 and an immune phage display library was constructed. After a multi-step panning, several antibody fragments (scFv, single chain fragment variable) with nanomolar affinities were isolated, that inhibited the endopeptidase activity of pure BoNT/E3 in vitro by targeting its light chain. Furthermore, three scFv were confirmed to neutralize BoNT/E3 induced paralysis in an ex vivo mouse phrenic nerve-hemidiaphragm assay. The most effective neutralization (20LD50/mL, BoNT/E3) was observed with scFv ELC18, with a minimum neutralizing concentration at 0.3 nM. Furthermore, ELC18 was highly effective in vivo when administered as an scFv-Fc construct. Complete protection of 1LD50 BoNT/E3 was observed with 1.6 ng/dose in the mouse flaccid paralysis assay.
conclusionThese scFv-Fcs antibodies are the first recombinant antibodies neutralizing BoNT/E by targeting its light chain. The human-like nature of the isolated antibodies is predicting a good tolerance for further clinical development.
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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.