The recombinant Hc subunit of Clostridium botulinum neurotoxin serotype A is an effective botulism vaccine candidate

Vaccine ◽  
2009 ◽  
Vol 27 (21) ◽  
pp. 2816-2822 ◽  
Author(s):  
Yun-Zhou Yu ◽  
Na Li ◽  
Heng-Qi Zhu ◽  
Rui-Lin Wang ◽  
Yun Du ◽  
...  
Keyword(s):  
Clostridium Botulinum ◽  
Botulinum Neurotoxin ◽  
Vaccine Candidate ◽  
Serotype A ◽  
Botulinum Neurotoxin Serotype A

Enhanced immune responses using plasmid DNA replicon vaccine encoding the Hc domain of Clostridium botulinum neurotoxin serotype A

Vaccine ◽  
2007 ◽  
Vol 25 (52) ◽  
pp. 8843-8850 ◽  
Author(s):  
Yun-Zhou Yu ◽  
Shu-Ming Zhang ◽  
Zhi-Wei Sun ◽  
Shuang Wang ◽  
Wei-Yuan Yu
Keyword(s):  
Immune Responses ◽  
Plasmid Dna ◽  
Clostridium Botulinum ◽  
Botulinum Neurotoxin ◽  
Serotype A ◽  
Botulinum Neurotoxin Serotype A

Easy expression of the C-terminal heavy chain domain of botulinum neurotoxin serotype A as a vaccine candidate using a bi-cistronic baculovirus system

2013 ◽  
Vol 189 (1) ◽  
pp. 58-64 ◽  
Author(s):  
Oliver B. Villaflores ◽  
Chein-Ming Hsei ◽  
Chao-Yi Teng ◽  
Ying-Ju Chen ◽  
Jiunn-Jye Wey ◽  
...  
Keyword(s):  
Heavy Chain ◽  
Botulinum Neurotoxin ◽  
Vaccine Candidate ◽  
Serotype A ◽  
Baculovirus System ◽  
Botulinum Neurotoxin Serotype A

A cyclic peptide–polymer probe for the detection of Clostridium botulinum neurotoxin serotype A

Toxicon ◽  
2006 ◽  
Vol 47 (8) ◽  
pp. 901-908 ◽  
Author(s):  
Hongzheng Ma ◽  
Bin Zhou ◽  
YoungSoo Kim ◽  
Kim D. Janda
Keyword(s):  
Clostridium Botulinum ◽  
Botulinum Neurotoxin ◽  
Cyclic Peptide ◽  
Serotype A ◽  
Botulinum Neurotoxin Serotype A

scholarly journals Characterization of clostridium botulinum neurotoxin serotype A (BoNT/A) and fibroblast growth factor receptor interactions using novel receptor dimerization assay

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nicholas G. James ◽  
Shiazah Malik ◽  
Bethany J. Sanstrum ◽  
Catherine Rhéaume ◽  
Ron S. Broide ◽  
...  
Keyword(s):  
Clostridium Botulinum ◽  
Botulinum Neurotoxin ◽  
Specific Binding ◽  
Rank Order ◽  
Neuromuscular Disorders ◽  
Growth Factor Receptor ◽  
Indirect Measure ◽  
Receptor Dimerization ◽  
Serotype A ◽  
Botulinum Neurotoxin Serotype A

AbstractClostridium botulinum neurotoxin serotype A (BoNT/A) is a potent neurotoxin that serves as an effective therapeutic for several neuromuscular disorders via induction of temporary muscular paralysis. Specific binding and internalization of BoNT/A into neuronal cells is mediated by its binding domain (HC/A), which binds to gangliosides, including GT1b, and protein cell surface receptors, including SV2. Previously, recombinant HC/A was also shown to bind to FGFR3. As FGFR dimerization is an indirect measure of ligand-receptor binding, an FCS & TIRF receptor dimerization assay was developed to measure rHC/A-induced dimerization of fluorescently tagged FGFR subtypes (FGFR1-3) in cells. rHC/A dimerized FGFR subtypes in the rank order FGFR3c (EC50 ≈ 27 nM) > FGFR2b (EC50 ≈ 70 nM) > FGFR1c (EC50 ≈ 163 nM); rHC/A dimerized FGFR3c with similar potency as the native FGFR3c ligand, FGF9 (EC50 ≈ 18 nM). Mutating the ganglioside binding site in HC/A, or removal of GT1b from the media, resulted in decreased dimerization. Interestingly, reduced dimerization was also observed with an SV2 mutant variant of HC/A. Overall, the results suggest that the FCS & TIRF receptor dimerization assay can assess FGFR dimerization with known and novel ligands and support a model wherein HC/A, either directly or indirectly, interacts with FGFRs and induces receptor dimerization.

scholarly journals Pure Botulinum Neurotoxin Is Absorbed from the Stomach and Small Intestine and Produces Peripheral Neuromuscular Blockade

1999 ◽  
Vol 67 (9) ◽  
pp. 4708-4712 ◽  
Author(s):  
Andrew B. Maksymowych ◽  
Marco Reinhard ◽  
Carl J. Malizio ◽  
Michael C. Goodnough ◽  
Eric A. Johnson ◽  
...  
Keyword(s):  
Small Intestine ◽  
Mouse Model ◽  
Heavy Chain ◽  
Clostridium Botulinum ◽  
General Circulation ◽  
Botulinum Neurotoxin ◽  
Serotype A ◽  
Relative Absorption ◽  
Botulinum Neurotoxin Serotype A

ABSTRACT Clostridium botulinum serotype A produces a neurotoxin composed of a 100-kDa heavy chain and a 50-kDa light chain linked by a disulfide bond. This neurotoxin is part of a ca. 900-kDa complex, formed by noncovalent association with a single nontoxin, nonhemagglutinin subunit and a family of hemagglutinating proteins. Previous work has suggested, although never conclusively demonstrated, that neurotoxin alone cannot survive passage through the stomach and/or cannot be absorbed from the gut without the involvement of auxiliary proteins in the complex. Therefore, this study compared the relative absorption and toxicity of three preparations of neurotoxin in an in vivo mouse model. Equimolar amounts of serotype A complex with hemagglutinins, complex without hemagglutinins, and purified neurotoxin were surgically introduced into the stomach or into the small intestine. In some experiments, movement of neurotoxin from the site of administration was restricted by ligation of the pylorus. Comparison of relative toxicities demonstrated that at adequate doses, complex with hemagglutinins, complex without hemagglutinins, and pure neurotoxin can be absorbed from the stomach. The potency of neurotoxin in complex was greater than that of pure neurotoxin, but the magnitude of this difference diminished as the dosage of neurotoxin increased. Qualitatively similar results were obtained when complex with hemagglutinins, complex without hemagglutinins, and pure neurotoxin were placed directly into the intestine. This work establishes that pure botulinum neurotoxin serotype A is toxic when administered orally. This means that pure neurotoxin does not require hemagglutinins or other auxiliary proteins for absorption from the gastrointestinal system into the general circulation.

scholarly journals Structures of Clostridium botulinum Neurotoxin Serotype A Light Chain Complexed with Small-Molecule Inhibitors Highlight Active-Site Flexibility

2007 ◽  
Vol 14 (5) ◽  
pp. 533-542 ◽  
Author(s):  
Nicholas R. Silvaggi ◽  
Grant E. Boldt ◽  
Mark S. Hixon ◽  
Jack P. Kennedy ◽  
Saul Tzipori ◽  
...  
Keyword(s):  
Small Molecule ◽  
Light Chain ◽  
Active Site ◽  
Clostridium Botulinum ◽  
Botulinum Neurotoxin ◽  
Small Molecule Inhibitors ◽  
Serotype A ◽  
Botulinum Neurotoxin Serotype A

scholarly journals Analysis of Neurotoxin Cluster Genes in Clostridium botulinum Strains Producing Botulinum Neurotoxin Serotype A Subtypes

2008 ◽  
Vol 74 (9) ◽  
pp. 2778-2786 ◽  
Author(s):  
Mark J. Jacobson ◽  
Guangyun Lin ◽  
Brian Raphael ◽  
Joanne Andreadis ◽  
Eric A. Johnson
Keyword(s):  
Amino Acid ◽  
Clostridium Botulinum ◽  
Botulinum Neurotoxin ◽  
Amino Acid Sequences ◽  
Gene Sequences ◽  
Amino Acid Levels ◽  
Cluster Type ◽  
Botulinum Neurotoxin Serotype A ◽  
Cluster Gene ◽  
Degree Of Similarity

ABSTRACT Neurotoxin cluster gene sequences and arrangements were elucidated for strains of Clostridium botulinum encoding botulinum neurotoxin (BoNT) subtypes A3, A4, and a unique A1-producing strain (HA− Orfx+ A1). These sequences were compared to the known neurotoxin cluster sequences of C. botulinum strains that produce BoNT/A1 and BoNT/A2 and possess either a hemagglutinin (HA) or an Orfx cluster, respectively. The A3 and HA− Orfx+ A1 strains demonstrated a neurotoxin cluster arrangement similar to that found in A2. The A4 strain analyzed possessed two sets of neurotoxin clusters that were similar to what has been found in the A(B) strains: an HA cluster associated with the BoNT/B gene and an Orfx cluster associated with the BoNT/A4 gene. The nucleotide and amino acid sequences of the neurotoxin cluster-specific genes were determined for each neurotoxin cluster and compared among strains. Additionally, the ntnh gene of each strain was compared on both the nucleotide and amino acid levels. The degree of similarity of the sequences of the ntnh genes and corresponding amino acid sequences correlated with the neurotoxin cluster type to which the ntnh gene was assigned.

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