Structure and action of clostridium botolinum neurotoxin and the use of recombinant vaccine technology in preventing animal botulism

Professorial Chair Lecture

Southern California Filipino Veterinary Medical Association Professorial Chair Lecture in Veterinary Medicine

Place

Department of Veterinary Paraclinical, College of Veterinary Medicine, UPLB

Date

6-23-2006

Abstract

Clostridium botulinum produce seven antigenically distinct neurotoxins designated as botulinum neurotoxins (BoNT) A through G. Each neurotoxin type is released in the form of multimeric complexes termed as progenitor toxins which consist of non-toxic components and the 150 kDa neurotoxin. This 150 kDa neurotoxin has three functional domains which are structurally and functionally distinct: the 50 kDa carboxy-terminal end is the translocation domain. The 50 kDa light chain is the catalytic domain which cleaves the protein complex involved in vesicle exocytosis for acetylcholine release. Inhibition of the release of this neurotransmitter results in the characteristic clinical manifestation of botulism which is flaccid paralysis.

Botulism occurs worldwide in both humans and animals, and is most often due to the ingestion of contaminated food or feeds. In humans, protection is provided by a pentavalent botulinum toxoid (PBT) against serotypes A through E. In animals, particularly in cattle, a bivalent form of the vaccine against types C and D is available (Brown et al., 1999). Conventional production of toxoid, however, is considered time-consuming, costly, hazardous and with issues of safety in end-users. These drawbacks led researchers to develop new methods for vaccine production against BoNTs which were largely directed by what is known about the neurotoxin's ultrastructure and function. An example is the production of synthetic carboxy-terminal end of the heavy chain (Hc) which is intended to induce antibodies against the binding domain, a critical intervention to prevent the subsequent process of translocation and inhibition of neurotransmitter release. Since the advent of this technology, recombinant vaccines with evident protection in mice have been produced for botulinum neurotoxin type A (LaPenotiere et al., 1993; Clayton et al., 1995; Byrne et al., Smith, 1998; Potter et al., 2000), type B (Potter et al., 1998), type F (Byrne et al., 2000; Holley et al., 2001) and types C and D (Woodward et al., 2003). The latter was recently shown to be promising as a bivalent, adjuvanted recombinant subunit vaccine in its target species, the bovine, with protection levels reaching up to 16000 MLD and 100 MLD protection levels per ml of serum, for neurotoxin types C and D, respectively.

Location

UPLB Main Library Special Collections Section (USCS)

College

College of Veterinary Medicine (CVM)

Language

English

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