Studies on the protective efficacy of recombinant truncated Hc from Clostridium botulinum neurotoxin A

Toxicon ◽  
1995 ◽  
Vol 33 (3) ◽  
pp. 297-298
Author(s):  
L. Smith ◽  
M. Zuber ◽  
T. Hoover
Keyword(s):  
Clostridium Botulinum ◽  
Botulinum Neurotoxin ◽  
Protective Efficacy ◽  
Botulinum Neurotoxin A

scholarly journals Intratracheal inoculation of AHc vaccine induces protection against aerosolized botulinum neurotoxin A challenge in mice

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Changjiao Gan ◽  
Wenbo Luo ◽  
Yunzhou Yu ◽  
Zhouguang Jiao ◽  
Sha Li ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Clostridium Botulinum ◽  
Freeze Drying ◽  
Botulinum Neurotoxin ◽  
Secretory Iga ◽  
Immune Protection ◽  
Dry Powder ◽  
Botulinum Neurotoxin A ◽  
Spray Freeze Drying

AbstractBotulinum neurotoxin (BoNT), produced by Clostridium botulinum, is generally known to be the most poisonous of all biological toxins. In this study, we evaluate the protection conferred by intratracheal (i.t.) inoculation immunization with recombinant Hc subunit (AHc) vaccines against aerosolized BoNT/A intoxication. Three AHc vaccine formulations, i.e., conventional liquid, dry powder produced by spray freeze drying, and AHc dry powder reconstituted in water are prepared, and mice are immunized via i.t. inoculation or subcutaneous (s.c.) injection. Compared with s.c.-AHc-immunized mice, i.t.-AHc-immunized mice exhibit a slightly stronger protection against a challenge with 30,000× LD50 aerosolized BoNT/A. Of note, only i.t.-AHc induces a significantly higher level of toxin-neutralizing mucosal secretory IgA (SIgA) production in the bronchoalveolar lavage of mice. In conclusion, our study demonstrates that the immune protection conferred by the three formulations of AHc is comparable, while i.t. immunization of AHc is superior to s.c. immunization against aerosolized BoNT/A intoxication.

scholarly journals Closed Genome Sequence of Clostridium botulinum Strain CFSAN064329 (62A)

2018 ◽  
Vol 6 (26) ◽  
Author(s):  
Travis G. Wentz ◽  
Kuan Yao ◽  
Kristin M. Schill ◽  
N. Rukma Reddy ◽  
Guy E. Skinner ◽  
...  
Keyword(s):  
Genome Sequence ◽  
Clostridium Botulinum ◽  
Botulinum Neurotoxin ◽  
Food Challenge ◽  
Strictly Anaerobic ◽  
Botulinum Neurotoxin A ◽  
Gram Positive ◽  
Content Type

Clostridium botulinum is a strictly anaerobic, Gram-positive, spore-forming bacterium that produces botulinum neurotoxin, a potent and deadly proteinaceous exotoxin. Clostridium botulinum strain CFSAN064329 (62A) produces an A1 serotype/subtype botulinum neurotoxin and is frequently utilized in food challenge and detection studies.

scholarly journals Evaluation of a Recombinant Hc of Clostridium botulinum Neurotoxin Serotype F as an Effective Subunit Vaccine

2008 ◽  
Vol 15 (12) ◽  
pp. 1819-1823 ◽  
Author(s):  
Yun-Zhou Yu ◽  
Na Li ◽  
Rui-Lin Wang ◽  
Heng-Qi Zhu ◽  
Shuang Wang ◽  
...  
Keyword(s):  
Clostridium Botulinum ◽  
Subunit Vaccine ◽  
Botulinum Neurotoxin ◽  
Protective Efficacy ◽  
Intraperitoneal Administration ◽  
Neutralization Assay ◽  
Gene Encoding ◽  
E Coli ◽  
Protective Antibodies ◽  
New Gene

ABSTRACT A new gene encoding the Hc domain of Clostridium botulinum neurotoxin serotype F (FHc) was designed and completely synthesized with oligonucleotides. A soluble recombinant Hc of C. botulinum neurotoxin serotype F was highly expressed in Escherichia coli with this synthetic FHc gene. Subsequently, the purified FHc was used to vaccinate mice and evaluate their survival against challenge with active botulinum neurotoxin serotype F (BoNT/F). After the administration of FHc protein mixed with Freund adjuvant via the subcutaneous route, a strong protective immune response was elicited in the vaccinated mice. Mice that were given two or three vaccinations with a dosage of 1 or 10 μg of FHc were completely protected against an intraperitoneal administration of 20,000 50% lethal doses (LD50) of BoNT/F. The BoNT/F neutralization assay showed that the sera from these vaccinated mice contained high titers of protective antibodies. Furthermore, mice were vaccinated once, twice, or three times at four different dosages of FHc using Alhydrogel (Sigma) adjuvant via the intramuscular route and subsequently challenged with 20,000 LD50 of neurotoxin serotype F. A dose response was observed in both the antibody titer and the protective efficacy with increasing dosage of FHc and number of vaccinations. Mice that received one injection of 5 μg or two injections of ≥0.04 μg of FHc were completely protected. These findings suggest that the recombinant FHc expressed in E. coli is efficacious in protecting mice against challenge with BoNT/F and that the recombinant FHc subunit vaccine may be useful in humans.

Identification of novel inhibitors of botulinum neurotoxin A

Planta Medica ◽  
2015 ◽  
Vol 81 (11) ◽  
Author(s):  
C Yalamanchili ◽  
VK Manda ◽  
AG Chittiboyina ◽  
WA Harrell Jr ◽  
RP Webb ◽  
...  
Keyword(s):  
Botulinum Neurotoxin ◽  
Botulinum Neurotoxin A

Botulinumtoxin zur Behandlung von neuropathischen Schmerzen

2017 ◽  
Vol 36 (05) ◽  
pp. 315-323
Author(s):  
N. Üçeyler ◽  
C. Sommer
Keyword(s):  
Botulinum Neurotoxin ◽  
Neuropathische Schmerzen ◽  
Botulinum Neurotoxin A ◽  
Topische Therapien

ZusammenfassungDie Behandlung neuropathischer Schmerzen mit systemisch wirksamen oral verabreichten Pharmaka ist bei vielen Patienten wirksam, kann jedoch zu zentralnervösen unerwünschten Wirkungen wie Müdigkeit oder Schwindel führen. Daher sind in den letzten Jahren topische Therapien in das Zentrum der Aufmerksamkeit gerückt. Botulinumtoxin, etabliert in der Therapie von Dystonien und Spastik, wurde zunehmend bei Schmerzerkrankungen getestet, hierbei ist Botulinum-Neurotoxin A der am besten untersuchte Serotyp. Die häufigsten Indikationen waren Schmerzen im Trigeminusversorgungsbereich und periphere neuropathische Schmerzen. Bei den meisten Studien war Botulinum-Neurotoxin A Placebo deutlich überlegen. Präklinische Studien zum Wirkmechanismus erbrachten die Erkenntnis, dass neben dem erwarteten peripheren Effekt sehr wahrscheinlich auch eine zentrale Reduktion der Ausschüttung von exzitatorischen Neurotransmittern an der Wirkung beteiligt ist.

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