Antigenic sites on the HN domain of botulinum neurotoxin A stimulate protective antibody responses against active toxin

Ayyar, B. Vijayalakshmi; Tajhya, Rajeev B.; Beeton, Christine; Atassi, M. Zouhair

doi:10.1038/srep15776

Cited by 13 publications

(11 citation statements)

References 37 publications

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“…The other chain with a smaller molecular weight is a light chain (LC, MW = 50 kDa). The LC is a zinc-dependent proteolytic enzyme which contributes to the cleavage of SNAP-25 at the neuromuscular junction [ 15 , 25 , 26 ]. It had been observed by some investigators that new axonal branches formed around skeletal muscles that had been paralyzed by BoNT/A for three to four months [ 27 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Botulinum Neurotoxin Serotype a Heavy Chain on the Growth Related Proteins and Neurite Outgrowth after Spinal Cord Injury in Rats

Wang

Lan

et al. 2018

Toxins

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(1) Background: The botulinum toxin A (BoNT-A) heavy chain (HC) can stimulate the growth of primary motor neurites. (2) Methods: A recombinant BoNT/A HC was injected locally plus interval intrathecal catheter of BoNT/A HC to rats with ipsilateral semi-dissociated lumbar spinal cord injuries (SCIs). First, 2D gel with a silver nitrate stain was applied to detect the general pattern of protein expression. Growth associated protein 43 (GAP-43) and superior cervical ganglion 10 (SCG10) were chosen to represent the altered proteins, based on their molecular weight and pI, and were used to further detect their expression. Meanwhile, the neuronal processes were measured. The measurements of thermal hyperalgesia and grasp power at the ipsilateral hindlimb were used to evaluate spinal sensory and motor function, respectively. (3) Results: The local injection of BoNT/A HC followed by its intrathecal catheter intervally altered the spinal protein expression pattern after an SCI; protein expression was similar to normal levels or displayed a remarkable increase. The changes in the expression and distribution of phosphorylated growth associated protein 43(p-GAP 43) and superior cervical ganglion 10 (SCG 10) indicated that the administration of BoNT/A HC to the SCI significantly amplified the expression of p-GAP43 and SCG10 (p < 0.05). Meanwhile, the positive immunofluorescent staining for both p-GAP43 and SCG10 was mainly present near the rostral aspect of the injury, both in the cytoplasm and the neuronal processes. Moreover, the outgrowth of neurites was stimulated by the BoNT/A HC treatment; this was evident from the increase in neurite length, number of branches and the percentage of cells with neuronal processes. The results from the spinal function tests suggested that the BoNT/A HC did not affect sensation, but had a large role in improving the ipsilateral hindlimb grasp power (p < 0.05). (4) Conclusions: The local injection with the intermittent intrathecal administration of BoNT/A heavy chain to rats with SCI increased the local expression of GAP-43 and SCG 10, which might be affiliated with the regeneration of neuronal processes surrounding the injury, and might also be favorable to the relief of spinal motor dysfunction.

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Section: Introductionmentioning

confidence: 99%

The Effect of Botulinum Neurotoxin Serotype a Heavy Chain on the Growth Related Proteins and Neurite Outgrowth after Spinal Cord Injury in Rats

Wang

Lan

et al. 2018

Toxins

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“…To summarize, the immunogenicity potential of BoNT/A HC and LC domains were investigated extensively leading to important findings. The BoNT/A HN region has also been recently explored as a vaccine candidate indicating that the BoNT/A HN domain is a valuable region in generating protective antibodies [87]. In addition to those findings, the presence of the region connecting HCc and HCn, that has been defined as the interaction site with SV2 receptor [88], has been found essential for neutralizing antibodies generation [89].…”

Section: Enhance Adherence and Targeting Efficiencymentioning

confidence: 99%

Antibodies and vaccines against botulinum toxins: Available measures and novel approaches

Rasetti-Escargueil

Lemichez

Popoff

2021

Toxicon

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HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

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“…To summarize, the immunogenicity potential of BoNT/A HC and LC domains were investigated extensively leading to important findings. The BoNT/A HN region has also been recently explored as a vaccine candidate indicating that the BoNT/A HN domain is a valuable region in generating protective antibodies [87]. In addition to those findings, the presence of the region connecting HC c and HC n , that has been defined as the interaction site with SV2 receptor [88], has been found essential for neutralizing antibodies generation [89].…”

Section: Alternative Strategies For Improvement Of Mabs Neutralizamentioning

confidence: 99%

Antibodies and Vaccines against Botulinum Toxins: Available Measures and Novel Approaches

Rasetti-Escargueil

Popoff

2019

Toxins

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Botulinum neurotoxin (BoNT) is produced by the anaerobic, Gram-positive bacterium Clostridium botulinum. As one of the most poisonous toxins known and a potential bioterrosism agent, BoNT is characterized by a complex mode of action comprising: internalization, translocation and proteolytic cleavage of a substrate, which inhibits synaptic exocytotic transmitter release at neuro-muscular nerve endings leading to peripheral neuroparalysis of the skeletal and autonomic nervous systems. There are seven major serologically distinct toxinotypes (A–G) of BoNT which act on different substrates. Human botulism is generally caused by BoNT/A, B and E. Due to its extreme lethality and potential use as biological weapon, botulism remains a global public health concern. Vaccination against BoNT, although an effective strategy, remains undesirable due to the growing expectation around therapeutic use of BoNTs in various pathological conditions. This review focuses on the current approaches for botulism control by immunotherapy, highlighting the future challenges while the molecular underpinnings among subtypes variants and BoNT sequences found in non-clostridial species remain to be elucidated.

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Antigenic sites on the HN domain of botulinum neurotoxin A stimulate protective antibody responses against active toxin

Cited by 13 publications

References 37 publications

The Effect of Botulinum Neurotoxin Serotype a Heavy Chain on the Growth Related Proteins and Neurite Outgrowth after Spinal Cord Injury in Rats

The Effect of Botulinum Neurotoxin Serotype a Heavy Chain on the Growth Related Proteins and Neurite Outgrowth after Spinal Cord Injury in Rats

Antibodies and vaccines against botulinum toxins: Available measures and novel approaches

Antibodies and Vaccines against Botulinum Toxins: Available Measures and Novel Approaches

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