Abstract
Botulinum neurotoxins (BoNT) cause the flaccid paralysis of botulism by inhibiting the release of acetylcholine from motor neurons. There are seven serotypes of BoNT (A-G), with limited therapies, and no FDA approved vaccine for botulism. An investigational formalin-inactivated penta-serotype-BoNT/A-E toxoid vaccine was used to vaccinate people who are at high risk of contracting botulism. However, this formalin-inactivated penta-serotype-BoNT/A-E toxoid vaccine was losing potency and was discontinued. This article reviews the different vaccines being developed to replace the discontinued toxoid vaccine. These vaccines include DNA-based, viral vector-based, and recombinant protein-based vaccines. DNA-based vaccines include plasmids or viral vectors containing the gene encoding one of the BoNT heavy chain receptor binding domains (HC). Viral vectors reviewed are adenovirus, influenza virus, rabies virus, Semliki Forest virus, and Venezuelan Equine Encephalitis virus. Among the potential recombinant protein vaccines reviewed are HC, light chain-heavy chain translocation domain, and chemically or genetically inactivated holotoxin.
Highlights
Nucleic Acid-Based Vaccines against BotulismPlasmid- and viral-based vectors are being developed as platforms for vaccines against botulism
Botulinum neurotoxins (BoNT) cause the flaccid paralysis of botulism by inhibiting the release of acetylcholine from motor neurons
The CDC recognizes five forms of botulism [1]: Foodborne botulism, intoxication occurs upon eating foods contaminated with Botulinum neurotoxins
Summary
Plasmid- and viral-based vectors are being developed as platforms for vaccines against botulism. Several viral-based platforms have been developed to allow for expression of immunizing doses of. Plasmid-based vaccination protected mice from intraperitoneal challenge by BoNT/A where protection correlated with the generation of antibodies to HC. These early studies conceptually supported the development of DNA vaccination to neutralize toxin action, and the use of HC as a vaccine candidate, based upon ease and safety of production. Jathoul et al found the human ubiquitin C (UbC) promoter elicited high expression of HC/F and subsequently high HC/F antibody titers, which protected against a challenge by 10,000 MLD50 Units of BoNT/F [17] Plasmid-based vaccination may require multiple vaccinations to elicit protective antibody titers [20]
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