Vaccines against botulism

Medical College of Wisconsin, Microbiology and Molecular Genetics BSB-256, Milwaukee, WI 53226, USA.
Current opinion in microbiology (Impact Factor: 5.9). 06/2012; 15(3):317-24. DOI: 10.1016/j.mib.2012.05.009
Source: PubMed


The clostridial neurotoxins (CNTs) are the most toxic proteins for humans and include botulinum neurotoxins (BoNT) and tetanus neurotoxin (TeNT). CNT neurotropism is based upon the preferred binding and entry into neurons and specific cleavage of neuronal SNARE proteins. While chemically inactive TeNT toxoid remains an effect vaccine, the current pentavalent vaccine against botulism is in limited supply. Recent advances have facilitated the development of the next generation of BoNT vaccines, utilizing non-catalytic full-length BoNT or a subunit vaccine composed of the receptor binding domain of BoNT as immunogens. This review describes the issues and progress towards the production of a vaccine against botulism that will be effective against natural BoNT variants.

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    • "Furthermore, mosaic BoNTs exist, including BoNT/CD and BoNT/DC (Moriishi et al., 1996) and the recently discovered BoNT/FA toxin (Gonzalez-Escalona et al., 2014; Kalb et al., 2015). BoNTs A, B, E and F cause botulism in humans (Karalewitz and Barbieri, 2012; Rossetto et al., 2014) and rank amongst the most toxic substances known. "
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    ABSTRACT: Botulinum neurotoxin A causes botulism but is also used for medical and cosmetic applications. A detailed molecular understanding of BoNT/A - host receptor interactions is therefore fundamental for improving current clinical applications and for developing new medical strategies targeting human disorders. Towards this end, we recently solved an X-ray crystal structure of BoNT/A1 in complex with its neuronal protein receptor SV2C. Based on our findings, we discuss the potential implications for BoNT/A function. Copyright © 2015. Published by Elsevier Ltd.
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    ABSTRACT: Tetanus and botulinum neurotoxins, produced by anaerobic bacteria of the genus Clostridium, are the most toxic proteins known and are the sole responsible for the pathogenesis of tetanus and botulism. They enter peripheral cholinergic nerve terminals and cleave proteins of the neuroexocytosis apparatus causing a persistent, but reversible, inhibition of neurotransmitter release. Botulinum neurotoxins are used in the therapy of many human syndromes caused by hyperactive cholinergic nerve terminals. Here we focus on the many advances that were recently made on the understanding of their molecular mechanism of action and on their use in human therapy.
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