Vaccines against botulism

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.

► We describe the molecular properties of botulinum neurotoxin (BoNT) and tetanus neurotoxin (TeNT). ► We examine the history and current statue of vaccines against botulism. ► Future BoNT vaccines will utilize recombinant holo-BoNT toxoid and/or subunit vaccine strategies. ► Natural BoNT variants challenge the development of a pan-BoNT vaccine.