Botulinum type A toxin neutralisation by specific IgG and its fragments: A comparison of mouse systemic toxicity and local flaccid paralysis assays

Jones, R. L.; Alsop, T.-A.; Hull, Robin; Tierney, Robert J.; Rigsby, Peter; Holley, Jane L.; Sesardic, Dorothea

doi:10.1016/j.toxicon.2006.05.007

Cited by 28 publications

(23 citation statements)

References 29 publications

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“…The healthy animals (horses) were immunized at an interval of every 3 days for 2 weeks and the antibody titer in blood was estimated by ELISA [32][33][34][35]. After 2 weeks, 10 ml of hyperimmune plasma was collected (test bleed) from each immunized animals and antibody titer value (potency) in plasma was estimated by rabies antigen neutralization using Swiss albino mice [36][37][38]. Based on the results of test bleed, animals were bled and hyperimmunised plasma was collected in sterilized nonpyrogenic glass container containing anticoagulant acid citrate dextrose (ACD).…”

Section: Collection Of Hyperimmune Plasmamentioning

confidence: 99%

Chromatographic purification of equine immunoglobulin G F(ab)2 from plasma

Fernandes

Kaundinya²,

Daftary

et al. 2008

Journal of Chromatography B

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Section: Collection Of Hyperimmune Plasmamentioning

confidence: 99%

Chromatographic purification of equine immunoglobulin G F(ab)2 from plasma

Fernandes

Kaundinya²,

Daftary

et al. 2008

Journal of Chromatography B

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“…. Several in vivo simulation assays, such as the hemidiaphragm assay and local injection assays (WilderKofie et al 2011;Rasetti-Escargueil et al 2011b;Jones et al 2006), have been developed to reduce the number of animals used (hemidiaphragm assay) and/or the suffering of animals (local injection assays). These assays are excellent research tools, but they still require the use of large numbers of animals and technical skills that make them unsuitable for mediumthroughput applications such as potency determination of BoNTs or antibody screening.…”

Section: Overview Of the Detection Of Bontsmentioning

confidence: 99%

Progress in Cell Based Assays for Botulinum Neurotoxin Detection

Pellett¹

2012

Current Topics in Microbiology and Immunology

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Botulinum neurotoxins (BoNTs) are the most potent human toxins known and the causative agent of botulism, and are widely used as valuable pharmaceuticals. The BoNTs are modular proteins consisting of a heavy chain and a light chain linked by a disulfide bond. Intoxication of neuronal cells by BoNTs is a multi-step process including specific cell binding, endocytosis, conformational change in the endosome, translocation of the enzymatic light chain into the cells cytosol, and SNARE target cleavage. The quantitative and reliable potency determination of fully functional BoNTs produced as active pharmaceutical ingredient (API) requires an assay that considers all steps in the intoxication pathway. The in vivo mouse bioassay has for years been the 'gold standard' assay used for this purpose, but it requires the use of large numbers of mice and thus causes associated costs and ethical concerns. Cell-based assays are currently the only in vitro alternative that detect fully functional BoNTs in a single assay and have been utilized for years for research purposes. Within the last 5 years, several cell-based BoNT detection assays have been developed that are able to quantitatively determine BoNT potency with similar or greater sensitivity than the mouse bioassay. These assays now offer an alternative method for BoNT potency determination. Such quantitative and reliable BoNT potency determination is a crucial step in basic research, in the development of pharmaceutical BoNTs, and in the quantitative detection of neutralizing antibodies.

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“…They are still refined in vivo assays, but nonlethal and with greatly reduced suffering of animals. These assays measure the local paralysis induced by BoNT, e.g., flaccid paralysis (Sesardic et al 1996;Jones et al 2006), abdominal ptosis (Takahashi et al 1990), hind limp paralysis (Sugiyama et al 1975;Pearce et al 1994;Aoki 2001), grip strength (Meyer et al 1979;Torii et al 2011), and toe-spread reflex (Wilder-Kofie et al 2011). Other assays use an electromyographic measurement of the compound action muscle potential to quantify BoNT activity or anti-BoNT antibodies (Sakamoto et al 2009;Torii et al 2010a, b).…”

Section: In Vivo and Ex Vivo Testsmentioning

confidence: 99%

“…Generally, these in vivo assays have not been used frequently for the detection of BoNT out of complex food, environmental, or clinical samples. Rather they have been used to quantify BoNT from pharmaceutical-grade toxin preparations (Huber et al 2008) or for the detection of antibodies against BoNT (Sesardic et al 2004;Jones et al 2006). However, these assays still require several days to perform and are in vivo tests with more or less objective readouts.…”

Section: In Vivo and Ex Vivo Testsmentioning

confidence: 99%

Complexity of Botulinum Neurotoxins: Challenges for Detection Technology

Dorner

Schulz

Kull

et al. 2012

Current Topics in Microbiology and Immunology

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The detection of botulinum neurotoxins (BoNT) is extremely challenging due to their high toxicity and the multiple BoNT variants. To date, seven serotypes with more than 30 subtypes have been described, and even more subtypes are expected to be discovered. The fact that the BoNT molecules are released as large complexes of different size and composition adds further complexity to the issue. Currently, in the diagnostics of botulism, the mouse bioassay (MBA) is still considered as gold standard for the detection of BoNT in complex sample materials. Over the years, different functional, immunological, and spectrometric assays or combinations thereof have been developed, supplemented by DNA-based assays for the detection of the organism. In this review, advantages and limitations of the current technologies will be discussed, highlighting some of the intricacies of real sample analysis.

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Botulinum type A toxin neutralisation by specific IgG and its fragments: A comparison of mouse systemic toxicity and local flaccid paralysis assays

Cited by 28 publications

References 29 publications

Chromatographic purification of equine immunoglobulin G F(ab)2 from plasma

Chromatographic purification of equine immunoglobulin G F(ab)2 from plasma

Progress in Cell Based Assays for Botulinum Neurotoxin Detection

Complexity of Botulinum Neurotoxins: Challenges for Detection Technology

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