Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2024-12-28T20:57:09.895Z Has data issue: false hasContentIssue false

Chapter 4 - Immunological Properties of Botulinum Neurotoxins

Published online by Cambridge University Press:  02 November 2023

By
Hans Bigalke ,
Dirk Dressler  and
Jürgen Frevert
Edited by
Daniel Truong ,
Dirk Dressler ,
Mark Hallett ,
Christopher Zachary  and
Mayank Pathak
Daniel Truong
Affiliation:
University of California, Riverside
Dirk Dressler
Affiliation:
Hannover Medical School
Mark Hallett
Affiliation:
National Institutes of Health (NIH)
Christopher Zachary
Affiliation:
University of California, Irvine
Mayank Pathak
Affiliation:
Truong Neuroscience Institute
Get access

Summary

Botulinum neurotoxin is used to treat a large number of muscle hyperactivity disorders, including dystonia, spasticity, and tremor; autonomic disorders such as hyperhidrosis, hypersalivation and various bladder disorders; and pain conditions, especially chronic migraine. Aesthetic applications have also become a large indication. Commercially available preparations of Bont/A and BoNT/B are listed.

The active component in all products is BoNT, a di-chain protein of 150 000 daltons. BoNT/A inhibits release of acetylcholine by cleaving the SNARE protein SNAP-25 while BoNT/B cleaves VAMP II. Since BoNT is a foreign protein, the human immune system may respond to it with the production of specific anti-BoNT antibodies (BoNT-AB).

The probability of developing BoNT-AB increases with the amount of BoNT applied at each injection series. Other drug- and patient-related factors might contribute to the immune response. Unspecific activation of the immune system as a possible risk factor for BoNT-AB formation is currently been discussed in connection with COVID-19 vaccination programs. A pre-activation of lymphocytes may have triggered BoNT/A-AB formation. In this chapter, a method is presented for the quantification of BoNT-AB in sera, the immune cell reactions to antigens are described and drug related immune responses are discussed.

Keywords

anti-BoNT antibodiesBoNT-ABmouse bioassaymouse diaphragm assaycomplexing proteinsneutralizing antibodies
Type
Chapter
Information
Manual of Botulinum Toxin Therapy , pp. 18 - 22
Publisher: Cambridge University Press
Print publication year: 2023

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Albrecht, P, Jansen, A, Lee, JI, et al. (2019). High prevalence of neutralizing antibodies after lone-term botulinum neurotoxin therapy. Neurology, 92, e48–e54.CrossRefGoogle Scholar
Aoki, KR (2002). Immunological and other properties of therapeutic botulinum toxin serotypes. In Brin, MF, Jankovic, J, Hallett, M (eds.) Scientific and Therapeutic Aspects of Botulinum Toxin. Philadelphia: Lippincott Williams & Wilkins, pp. 103–13.Google Scholar
Atassi, MZ (2006). On the enhancement of anti-neurotoxin antibody production by subcomponents HA1 and HA3b of Clostridium botulinum type B 16S toxin-haemagglutinin. Microbiology,152, 1891–95.Google Scholar
Bigalke, H, Dressler, D, Frevert, J (2022). Immunological properties of botulinum neurotoxins. Clin Park Relat Disord, In press.Google Scholar
Blümel, J, Frevert, J, Schwaier, A (2006). Comparative antigenicity of botulinum neurotoxin type A in the rabbit [Abstract]. Neurotox Res, 9, 238.Google Scholar
Boehncke, WH, Brembilla, NC (2018). Immunogenicity of biologic therapies: causes and consequences. Expert Rev Clin Immunol, 14, 513–23.CrossRefGoogle ScholarPubMed
Callaway, JE (2004). Botulinum toxin type B (Myobloc): pharmacology and biochemistry. Clin Dermatol, 22, 23–8.CrossRefGoogle ScholarPubMed
Choi, NW, Estes, MK, Langridge, WH (2006). Ricin toxin B subunit enhancement of rotavirus NSP4 immunogenicity in mice. Viral Immunol, 19, 54–63.CrossRefGoogle ScholarPubMed
Dressler, D (2006). Pharmacological aspects of therapeutic botulinum toxin preparations. Nervenarzt, 77, 912–21.CrossRefGoogle ScholarPubMed
Dressler, D, Lange, M, Bigalke, H (2005). The mouse diaphragm assay for detection of antibodies against botulinum toxin type B. Mov Disord, 20, 1617–19.CrossRefGoogle ScholarPubMed
Dressler, D, Hallett, M (2006). Immunological aspects of Botox, Dysport and Myobloc/NeuroBloc. Eur J Neurol, 13 (Suppl 1), 11–15.CrossRefGoogle ScholarPubMed
Dressler, D, Wohlfahrt, K, Meyer-Rogge, E, Wiest, L, Bigalke, H (2011). Antibody-induced botulinum toxin therapy failure in dermal indications. Dermatol Surg, 36 (Suppl 4), 2182–7.Google Scholar
Dressler, D, Tacik, P, Adib Saberi, F (2014). Botulinum toxin therapy of cervical dystonia: duration of therapeutic effects. J Neural Transm, 122, 297–300.CrossRefGoogle ScholarPubMed
Dressler, D, Pan, L, Adib Saberi, F (2018). Antibody-induced failure of botulinum toxin therapy: re-start with low-antigenicity drugs offers a new treatment opportunity. J Neural Transm, 125,1481–6.CrossRefGoogle ScholarPubMed
Frevert, J (2010). Content of botulinum neurotoxin in Botox/Vistabel, Dysport/Azzalure, and Xeomin/Bocouture. Drugs R D, 10,67–73.CrossRefGoogle ScholarPubMed
Goschel, H, Wohlfarth, K, Frevert, J, Dengler, R, Bigalke, H (1997). Botulinum A toxin therapy: neutralizing and nonneutralizing antibodies-therapeutic consequences. Exp Neurol, 147, 96–102.CrossRefGoogle ScholarPubMed
Hajam, IA, Dar, PA, Shahnawaz, I, Jaume, JC, Lee, JH (2017). Bacterial flagellin-a potent immunomodulatory agent. Exp Mol Med, 49, e373.Google Scholar
Lange, O, Bigalke, H, Dengler, R et al. (2009). Neutralizing antibodies and secondary therapy failure after treatment with botulinum toxin type A: much ado about nothing? Clin Neuropharmacol, 32, 213–18.Google Scholar
Lee, JC, Yokota, K, Arimitsu, H et al. (2005). Production of anti-neurotoxin antibody is enhanced by two subcomponents, HA1 and HA3b, of Clostridium botulinum type B 16S toxin-haemagglutinin. Microbiol, 151, 3739–47.CrossRefGoogle ScholarPubMed
Lee, SE, Kim, SY, Jeong, BC et al. (2006). A bacterial flagellin, Vibrio vulnificus FlaB, has a strong mucosal adjuvant activity to induce protective immunity. Infect Immun, 74, 694–702.CrossRefGoogle Scholar
Matsumura, T, Fujinaga, Y (2020). Functional analysis of botulinum hemagglutinin (HA). Methods Mol Biol, 2132, 191–200.CrossRefGoogle ScholarPubMed
Oshima, M, Deitiker, PR, Jankovic, J et al. (2011). Human T-cell responses to botulinum neurotoxin: proliferative responses in vitro of lymphocytes from botulinum neurotoxin A-treated movement disorder patients. J Neuroimmunol, 237, 66–72.CrossRefGoogle ScholarPubMed
Panjwani, N, O’Keeffe, R, Pickett, A (2008). Biochemical, functional and potency characteristics of type A botulinum toxin in clinical use. Botulinum J, 1(1), 153–66.CrossRefGoogle Scholar
Prawdzik, G, Oliyai, C, Joshi, A (2018). Nonclinical overview of daxibotulinumtoxinA for injection to support registration for human use. Toxicon, 156, S94.CrossRefGoogle Scholar
Reyna-Margarita, HR, Irais, CM, Mario-Alberto, RG et al. (2019). Plant phenolics and lectins as vaccine adjuvants. Curr Pharm Biotechnol, 20, 1236–43.Google Scholar
Shankar, G, Pendley, C, Stein, KE (2007). A risk-based bioanalytical strategy for the assessment of antibody immune responses against biological drugs. Nat Biotechnol, 25, 555–61.Google Scholar
Siegel, LS (1989). Evaluation of neutralizing antibodies to type A, B, E, and F botulinum toxins in sera from human recipients of botulinum pentavalent (ABCDE) toxoid. J Clin Microbiol, 27, 1906–8.CrossRefGoogle Scholar
Wohlfarth, K, Goschel, H, Frevert, J, Dengler, R, Bigalke, H (1997). Botulinum A toxins: units versus units. Naunyn-Schmiedeberg’s Arch Pharmacol, 355, 335–40.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×