Vaccines against Botulism

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.

Immunogenicity of a Bivalent Non-Purified Recombinant Vaccine against Botulism in Cattle

“…Although these are effective on conferring protection, toxoids are time-consuming to prepare and are potentially hazardous during detoxification [ 11 ]. Therefore, the development of recombinant subunit vaccines has been evaluated as a mean of solving these problems [ 12 , 16 , 19 , 22 , 23 ].…”

“…Recombinant vaccines for BoNT types C and D would offer several advantages over the present vaccine such as low or no toxicity, good immunogenicity, the use of non-pathogenic strains, stable and predictable yield, making it easier to scale up production and eliminating the need for detoxification steps [ 16 ]. However, purifying recombinant proteins could involve very expensive chromatography steps, which can make the process unattractive for veterinary applications [ 17 , 18 ].…”

Biosecurity Threat Posed by Botulinum Toxin

“…In the past, an inactivated pentavalent botulinum toxoid (PBT) vaccine (A-E) [35] was used in the United States for the vaccination of persons at higher risk of contracting the disease, such as personnel of laboratories, research and manufacturing facilities. However, its use was discontinued in 2011, after a review of available data indicated a decline in the immunogenicity of some of the toxin serotypes and the occurrence of moderate local reactions related to annual boosters [36,37]. There are several candidate vaccines to replace the PBT vaccine, including recombinant protein-based, DNA-based and viral vector-based vaccines [37].…”

“…However, its use was discontinued in 2011, after a review of available data indicated a decline in the immunogenicity of some of the toxin serotypes and the occurrence of moderate local reactions related to annual boosters [36,37]. There are several candidate vaccines to replace the PBT vaccine, including recombinant protein-based, DNA-based and viral vector-based vaccines [37].…”

Engineering Botulinum Toxins to Improve and Expand Targeting and SNARE Cleavage Activity

“…In addition to the therapeutic opportunities afforded by the application of recombinant techniques to BoNT engineering and manufacture, a second vital application opportunity is in the field of vaccine production [ 40 , 41 ]. For many years, researchers have explored the use of domains/fragments of BoNT as candidates for the preparation of new vaccines to BoNTs.…”