Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.69 (botulinum neurotoxin)
1,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

On January 16, 1997 two Germans got botulism after eating hot-smoked Canadian whitefish produced in Finland. The serum sample of one of the patients contained 6 MLD/ml of botulinum toxin. The type of toxin was identified as E by the toxin neutralization test and the botulinum neurotoxin type E (BoNT/E) gene was also amplified from the serum by polymerase chain reaction (PCR), but C. botulinum could not be isolated from the positive serum sample. The remains of the hot-smoked whitefish eaten by the patients contained botulinum toxin detected by the mouse bioassay and the BoNT/E gene as determined by PCR. C. botulinum was isolated from the fish sample and it was confirmed to be type E by the mouse bioassay and by PCR. Eleven other fish samples from the same lot did not contain botulinum toxin nor any BoNT gene. The incriminated food was processed on the 9th and 10th of January, 1997 from frozen whitefish imported to Finland from Canada. The pulsed-field gel electrophoretic pattern of the isolated C. botulinum strain resembled a reference strain of North American origin. It did not match any C. botulinum strains isolated from the Baltic sea-bottom or from the fish caught in the area indicating that the fish was contaminated by C. botulinum in Canada. The conditions resulting in toxin production could not be identified. The safety problems associated with vacuum-packaged hot-smoked fish seem to be of utmost concern and the product is one of the most important botulism food vehicles processed on an industrial scale. Temperature monitoring and the use of time-temperature indicators are to be recommended in order to ensure adequate storage temperature from processing through to consumption. Allowing the use of nitrate and nitrite together with sufficiently high NaC1 concentration in this particular product should also be considered.
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PMID:Type E botulism associated with vacuum-packaged hot-smoked whitefish. 976 32

A synthetic gene encoding the Hc (binding) domain of Clostridium botulinum neurotoxin F (FHc) was expressed in Escherichia coli fused to maltose binding protein (MBP). The purified MBP-FHc and FHc isolated after removal of MBP were evaluated in mice for their ability to protect against toxin challenge. Balb/c mice developed a protective immune response following administration of either protein via the intraperitoneal or intramuscular routes. A comparison of antibody titres and protection following single and multiple vaccinations and the effects of dosage are shown. The long term protection afforded by the vaccines was also investigated. Ten months following vaccination mice were still protected when challenged with 10(4) MLD(50) doses of botulinum toxin F.
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PMID:Cloning, expression and evaluation of a recombinant sub-unit vaccine against Clostridium botulinum type F toxin. 1093 Jun 84

A DNA vaccine was constructed which expressed the binding domain of Clostridium botulinum neurotoxin serotype F fused to a signal peptide. Three intra-muscular doses fully protected Balb/c mice against 10(4) MLD of serotype F toxin. Priming of the immune response by DNA vaccination followed by a single booster with type F binding domain protein resulted in high levels of antibody against the binding domain. This study demonstrates the utility of DNA vaccination for protection against botulinum neurotoxin type F and indicates that a prime-boost regimen could be an efficient method of generating antibody for passive immune therapy in cases of botulism involving serotype F toxin.
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PMID:DNA vaccination protects against botulinum neurotoxin type F. 1280 37

DNA vaccines which expressed the Hc fragment of the Clostridium botulinum type F neurotoxin (BoNT/F Hc) fused to a signal peptide downstream of four different eukaryotic promoters were prepared. Subsequently, the immunogenicity of the DNA vaccines and protection afforded in mice against challenge with 10(4) MLD of type F botulinum toxin was evaluated. The DNA vaccine containing the human ubiquitin gene (UbC) promoter induced the highest BoNT/F Hc-specific antibody concentration following two intramuscular immunisations and afforded 90% protection against challenge. The results from this study indicate that the selection of promoter used in DNA vaccination studies may be of importance in designing optimised vaccines.
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PMID:Efficacy of DNA vaccines expressing the type F botulinum toxin Hc fragment using different promoters. 1536 42

Botulinum neurotoxins cause botulism, a neuroparalytic disease in humans and animals. We constructed a replication-incompetent adenovirus encoding a synthesized codon-optimized gene for expression of the heavy chain C-fragment (H(C)50) of botulinum neurotoxin type C (BoNT/C). This recombinant human serotype 5 adenoviral vector (Ad5) was evaluated as a genetic vaccine candidate against botulism caused by BoNT/C in a mouse model. A one-time intramuscular injection with 10(5) to 2 x 10(7)pfu of adenoviral vectors elicited robust serum antibody responses against H(C)50 of BoNT/C as assessed by ELISA. Immune sera showed high potency in neutralizing the active BoNT/C in vitro. After a single dose of 2 x 10(7)pfu adenoviral vectors, the animals were completely protected against intraperitoneal challenge with 100 x MLD(50) of active BoNT/C. The protective immunity appeared to be vaccine dose-dependent. The anti-toxin protective immunity could last for at least 7 months without a booster injection. In addition, we observed that pre-existing immunity to the wild-type Ad5 in the host had no significant influence on the protective efficacy of vaccination. The data suggest that an adenovirus-vectored genetic vaccine is a highly efficient prophylaxis candidate against botulism.
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PMID:Protective immunity against botulism provided by a single dose vaccination with an adenovirus-vectored vaccine. 1789 56

A replication-incompetent adenoviral vector encoding the heavy chain C-fragment (H(C)50) of botulinum neurotoxin type C (BoNT/C) was evaluated as a mucosal vaccine against botulism in a mouse model. Single intranasal inoculation of the adenoviral vector elicited a high level of H(C)50-specific IgG, IgG1 and IgG2a in sera and IgA in mucosal secretions as early as 2 weeks after vaccination. The antigen-specific serum antibodies were maintained at a high level at least until the 27th week. Immune sera showed high potency in neutralizing BoNT/C as indicated by in vitro toxin neutralization assay. The mice receiving single dose of 2 x 10(7) p.f.u. (plaque-forming unit) of adenoviral vector were completely protected against challenge with up to 10(4) x MLD(50) of BoNT/C. The protective immunity showed vaccine dose dependence from 10(5) to 2 x 10(7) p.f.u. of adenoviral vector. In addition, animals receiving single intranasal dose of 2 x 10(7) p.f.u. adenoviral vector could be protected against 100 x MLD(50) 27 weeks after vaccination. Animals with preexisting immunity to adenovirus could also be vaccinated intranasally and protected against lethal challenge with BoNT/C. These results suggest that the adenoviral vector is a highly effective gene-based mucosal vaccine against botulism.
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PMID:An adenoviral vector-based mucosal vaccine is effective in protection against botulism. 1912 60