• Vaccine Name: BoNT/F(Hc)
• Target Pathogen: Clostridium botulinum
• Target Disease: Botulism
• Vaccine Ontology ID: VO_0004076
• Type: Toxoid vaccine
• Adjuvant:
  • Adjuvant name:
  • VO adjuvant ID: VO_0000127
  • Description: separate monovalent toxoid vaccine against BoNTF was manufactured for the U.S. Army by Porton Products Limited in cooperation with the United Kingdom Governments Center for Applied Microbiology and Research (CAMR) in 1990 (Byrne et al., 2000).
• Preparation: The vaccine batch no. 002/90 was derived from pooling three production lots of C. botulinum F toxin. The harvested toxin (i.e. by acid precipitation, tangential flow filtration, and centrifugation) from each of three fermentation runs was pooled and the type F toxin extracted with sodium phosphate buffer (PBS). After ribonuclease treatment, the toxin was further purified by ammonium sulfate precipitation, and repeated fractionation on fast liquid column chromatography on a fast flow Q Sepharose column. Unlike the toxoid (estimated toxoid purity of 10%), the purity of the type F botulinum toxoid Lot no. 002/90 was greater than 60% (IND 5077). The partially purified F toxin was formalin-detoxified and adsorbed to adjuvant (Byrne et al., 2000).
• Virulence: Even though toxoid vaccines are available, there are numerous shortcomings with their current use and ease of production. First, because C. botulinum is a spore-former, a dedicated facility is required to manufacture a toxin-based product. The requirement for a dedicated manufacturing facility is not trivial. It is extremely costly to renovate and upgrade an existing facility or to build a new one and then to maintain the facility in accordance with current Good Manufacturing Practices (cGMP) to manufacture one vaccine. Second, the yields of toxin production from C. botulinum are relatively low. Third, the toxoid-producing process involves handling large quantities of toxin and thus is dangerous, and the added safety precautions increase the cost of manufacturing. Fourth, the toxoid product for types A-E consists of a crude extract of clostridial proteins that may influence immunogenicity or reactivity of the vaccine, and the type F toxoid is only partially purified (IND 5077). Fifth, because the toxoid-producing process involves the use of formaldehyde, which inactivates the toxin, and residual levels of formaldehyde (not to exceed 0.02%) are part of the product formulation to prevent reactivation of the toxin, the vaccine is reactogenic. An additional component of the toxoid vaccines is the preservative thimerosal (0.01%), which also increases the reactogenicity of the product (Byrne et al., 2000).
• Description: A separate monovalent toxoid vaccine against BoNTF was manufactured for the U.S. Army by Porton Products Limited in cooperation with the United Kingdom Governments Center for Applied Microbiology and Research (CAMR) in 1990 (Byrne et al., 2000).

Mouse Response

• Host Strain: BALB/c
• Vaccination Protocol: Mice were injected with 50 μl inoculum into each hind leg of each mouse. All mice were tail bled for sera 1 day prior to toxin challenge. Mice were then challenged i.p. with 10^4 MLD of type F C. botulinum toxin (BoNT/F). Mice were challenged 28 d after their final vaccination. Untreated groups of age-matched mice were used as controls (Jathoul et al., 2004).
• Persistence: (Jathoul et al., 2004)
• Side Effects: None were noted (Jathoul et al., 2004).
• Efficacy: BoNT/F DNA vaccine provided 90% protection against 10^4 MLD BoNT/F in mice following two immunizations with 100 μg DNA (Jathoul et al., 2004).
• Description: A vaccine consisting of inactivated C. botulinum culture supernatants has been produced to provide military personnel with protection against BoNTs A, B, C, D and E. However, disadvantages associated with this vaccine include its expense and requirement for frequent boosters to maintain protection, as well as its efficacy against only 5 of the 7 BoNT types. Thus, new generation botulinum vaccines are being investigated, including the use of non-toxic BoNT Hc fragments as antigens. More recently, DNA vaccines encoding BoNT/A Hc and type F botulinum neurotoxin Hc fragment (BoNT/F Hc) have been evaluated as candidate next generation botulism vaccines. Such DNA vaccines may be optimized in terms of the regulatory elements used to drive expression of BoNT Hc (Jathoul et al., 2004).