Isolation and characterization of a neutralizing antibody specific to internalization domain of Clostridium botulinum neurotoxin type B

Yang, Gi-Hyeok; Kim, Kyu-Sik; Kim, Hak-Woo; Jeong, Sung Tae; Huh, Gyung Heng; Kim, Ji Cheon; Jung, Hyun Ho

doi:10.1016/j.toxicon.2004.03.016

Cited by 25 publications

(23 citation statements)

References 23 publications

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“…Recently, a monoclonal antibody that was specific for the translocation domain of BoNT/B was demonstrated to neutralize the toxin (36). This observation, in conjunction with the data presented in the current study, suggests that numerous steps in the intoxication process can act as targets for neutralization.…”

Section: Discussionsupporting

confidence: 83%

Subunit Vaccine against the Seven Serotypes of Botulism

et al. 2008

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Section: Discussionsupporting

confidence: 83%

Subunit Vaccine against the Seven Serotypes of Botulism

et al. 2008

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“…The isolated HC 50 domain retains affinity for neuromuscular junctions, and this affinity is typically quantified by measuring the ability of the polypeptide to antagonize the actions of the parent toxin. This functional assay ensures that the HC 50 activity being quantified is relevant to the neuroparalytic actions of the parent toxin (Lalli et al, 1999;Yang et al, 2004).…”

Section: Methodsmentioning

confidence: 99%

Evidence That Botulinum Toxin Receptors on Epithelial Cells and Neuronal Cells Are Not Identical: Implications for Development of a Non-Neurotropic Vaccine

Elias¹,

Al-Saleem²,

Ancharski³

et al. 2010

J Pharmacol Exp Ther

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Botulinum toxin typically interacts with two types of cells to cause the disease botulism. The toxin initially interacts with epithelial cells in the gut or airway to undergo binding, transcytosis, and delivery to the general circulation. The toxin then interacts with peripheral cholinergic nerve endings to undergo binding, endocytosis, and delivery to the cytosol. The receptors for botulinum toxin on nerve cells have been identified, but receptors on epithelial cells remain unknown. The initial toxin binding site on nerve cells is a polysialoganglioside, so experiments were performed to determine whether polysialogangliosides are also receptors on epithelial cells. A series of single mutant and dimutant forms of the botulinum toxin type A binding domain (HC 50 ) were cloned and expressed. One of these (dimutant HC 50 A W1266L,Y1267S ) was shown to have lost its ability to bind nerve cells (phrenic nerve-hemidiaphragm preparation), yet it retained its ability to bind and cross human epithelial monolayers (T-84 cells). In addition, the wild-type HC 50 and the dimutant HC 50 displayed the same ability to undergo binding and transcytosis (absorption) in a mouse model. The fact that the dimutant retained the ability to cross epithelial barriers but did not possess the ability to bind to nerve cells was exploited to create a mucosal vaccine that was non-neurotropic. The wild-type HC 50 and non-neurotropic HC 50 proved to be comparable in their abilities to: 1) evoke a circulating IgA and IgG response and 2) evoke protection against a substantial challenge dose of botulinum toxin.

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“…Analogous to antitoxins, neutralizing antibodies are capable of only sequestering freely circulating BoNTs and consequently become useless once the toxin has undergone endocytosis. [67] Two general techniques have been used to isolate the neutralizing mAbs against several of the BoNTs: 1) immunization of mice with toxoid or BoNT HC followed by standard hybridoma techniques [75][76][77][78] and 2) selection of mAbs against BoNTs or toxin fragments by using phage display technology. [79][80][81] Studies on the use of mAbs to target BoNTs have primarily focused on serotype A-likely because of its extreme potency and potential use as a bioweapon.…”

Section: Passive Vaccinesmentioning

confidence: 99%

The Strange Case of the Botulinum Neurotoxin: Using Chemistry and Biology to Modulate the Most Deadly Poison

et al. 2008

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In the classic novella "The Strange Case of Dr. Jekyll and Mr. Hyde", Robert Louis Stevenson paints a stark picture of the duality of good and evil within a single man. Botulinum neurotoxin (BoNT), the most potent known toxin, possesses an analogous dichotomous nature: It shows a pronounced morbidity and mortality, but it is used with great effect in much lower doses in a wide range of clinical scenarios. Recently, tremendous strides have been made in the basic understanding of the structure and function of BoNT, which have translated into widespread efforts towards the discovery of biomacromolecules and small molecules that specifically modulate BoNT activity. Particular emphasis has been placed on the identification of inhibitors that can counteract BoNT exposure in the event of a bioterrorist attack. This Review summarizes the current advances in the development of therapeutics, including vaccines, peptides, and small-molecule inhibitors, for the prevention and treatment of botulism.

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Isolation and characterization of a neutralizing antibody specific to internalization domain of Clostridium botulinum neurotoxin type B

Cited by 25 publications

References 23 publications

Subunit Vaccine against the Seven Serotypes of Botulism

Subunit Vaccine against the Seven Serotypes of Botulism

Evidence That Botulinum Toxin Receptors on Epithelial Cells and Neuronal Cells Are Not Identical: Implications for Development of a Non-Neurotropic Vaccine

The Strange Case of the Botulinum Neurotoxin: Using Chemistry and Biology to Modulate the Most Deadly Poison

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