ArticleThe Journal of infectious diseases2016
Immunological Characterization and Neutralizing Ability of Monoclonal Antibodies Directed Against Botulinum Neurotoxin Type H.
Article in The Journal of infectious diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Guideline
- Article
- Development of Effective Medical Countermeasures Against the Main Biowarfare Agents: The Importance of Antibodies.Microorganisms · 2024Review
- Isolation and characterization of Hc-targeting chimeric heavy chain antibodies neutralizing botulinum neurotoxin type B.Frontiers in immunology · 2024Article
- Biological and Immunological Characterization of a Functional L-HN Derivative of Botulinum Neurotoxin Serotype F.Toxins · 2023Article
- Clostridial Neurotoxins: Structure, Function and Implications to Other Bacterial Toxins.Microorganisms · 2021Review
- Closed Genome Sequence of Clostridium botulinum Strain IBCA10-7060 Type Bh.Microbiology resource announcements · 2021Article
- Fully Human Monoclonal Antibodies Effectively Neutralizing Botulinum Neurotoxin Serotype B.Toxins · 2020Article
- Adult Intestinal Toxemia Botulism.Toxins · 2020Review
- The Novel Clostridial Neurotoxin Produced by Strain IBCA10-7060 Is Immunologically Equivalent to BoNT/HA.Toxins · 2019Article
- Review
- Antibodies and Vaccines against Botulinum Toxins: Available Measures and Novel Approaches.Toxins · 2019Review
- Safety and Pharmacokinetics of a Four Monoclonal Antibody Combination Against Botulinum C and D Neurotoxins.Antimicrobial agents and chemotherapy · 2019Article
- Article
- mRNA: A Novel Avenue to Antibody Therapy?Molecular therapy : the journal of the American Society of Gene Therapy · 2019Review
- Natural Compounds and Their Analogues as Potent Antidotes against the Most Poisonous Bacterial Toxin.Applied and environmental microbiology · 2018Article
- Structural and biochemical characterization of the protease domain of the mosaic botulinum neurotoxin type HA.Pathogens and disease · 2018Article
- Substrate cleavage and duration of action of botulinum neurotoxin type FA ("H, HA").Toxicon : official journal of the International Society on Toxinology · 2018Article
- Review
- Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundOnly Clostridium botulinum strain IBCA10-7060 produces the recently described novel botulinum neurotoxin type H (BoNT/H). BoNT/H (N-terminal two-thirds most homologous to BoNT/F and C-terminal one-third most homologous to BoNT/A) requires antitoxin to toxin ratios ≥1190:1 for neutralization by existing antitoxins. Hence, more potent and safer antitoxins against BoNT/H are needed.
methodsWe therefore evaluated our existing monoclonal antibodies (mAbs) to BoNT/A and BoNT/F for BoNT/H binding, created yeast-displayed mutants to select for higher-affinity-binding mAbs by using flow cytometry, and evaluated the mAbs' ability to neutralize BoNT/H in the standard mouse bioassay.
resultsAnti-BoNT/A HCC-binding mAbs RAZ1 and CR2 bound BoNT/H with high affinity. However, only 1 of 6 BoNT/F mAbs (4E17.2A) bound BoNT/H but with an affinity >800-fold lower (equilibrium dissociation binding constant [KD] = 7.56 × 10(-8)M) than its BoNT/F affinity (KD= 9.1 × 10(-11)M), indicating that the N-terminal two-thirds of BoNT/H is immunologically unique. The affinity of 4E17.2A for BoNT/H was increased >500-fold to KD= 1.48 × 10(-10)M (mAb 4E17.2D). A combination of mAbs RAZ1, CR2, and 4E17.2D completely protected mice challenged with 280 mouse median lethal doses of BoNT/H at a mAb dose as low as 5 µg of total antibody.
conclusionsThis 3-mAb combination potently neutralized BoNT/H and represents a potential human antitoxin that could be developed for the prevention and treatment of type H botulism.
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