Vaccines for Clostridium botulinum
Treatment with antitoxin requires rapid identification of BoNT poisoning and weeks to months of supportive care after treatment. Moreover, antitoxin treatment is only effective for a few life-threatening botulinum cases and cannot be an effective prophylactic strategy for preventing intoxication of large-scale population threatened by weaponized C. botulinum toxin. Therefore, there is a need to proactively develop new therapies and vaccination strategies that can prevent intoxication.
Clostridium botulinum
Clostridium botulinum (C. botulinum) is a gram-positive spore-forming bacterium concerning as a class-I bioweapon and can be cultivated from the soil. Botulinum neurotoxins (BoNTs) are deadly, toxic proteins produced by the bacterium C. botulinum that can cause significant diseases in humans. The use of this poisonous substances as potential bioweapons has raised concerns by the Centers for Disease Control and Prevention and the United States Military. C. botulinum secretes neurotoxin serotype (A-H); however, human botulism is usually associated with toxin serotypes A, B, E, and F. These toxic BoNTs can lead to death through airway obstruction secondary to muscle paralysis.
Vaccines for Clostridium botulinum
- DNA Vaccines
- Subunit Vaccines
BoNT is a 150-kDa protein consisting of a 50-kDa light chain (L) and a 100-kDa heavy chain (H) linked by a disulfide bond. The toxins of all serotypes have a similar structure, and the receptor binding domain at the C-terminus (HC fragment) of the heavy chain is linked to its receptor and then internalized by endocytosis. The N-terminal heavy chain (HN) facilitates transport of the light chain (LC) across the endosomal membrane and into the cytosol. The novel monovalent vaccines and trivalent cocktail DNA vaccines targeting heavy chain C-terminal fragments of C. botulinum neurotoxin serotypes A, B, and E induce robust humoral and polyfunctional CD4+ T-cell immune responses which fully protected animals from lethal toxin challenge. DNA vaccines that target the receptor binding domain (Hc) may be effective prophylactic vaccines against botulinum. The safety, immunogenicity, and stability of DNA vaccines make it an option for specifically targeting botulinum antigens and allowing for stable delivery in any place where bioterrorism attack may occur.
BoNTs can enter the host by various means; however, the most common mode of entry is the orogastric route. Currently, treatment and prevention methods for BoNTs include the physical elimination of neurotoxins and providing basic care to sustain life, while anti-toxin antibody is considered the primary route of treatment. The HC of BoNT binds to the neuronal receptor SV2 and is used for internalization of toxins. Therefore, neutralizing antibodies against BoNT, particularly Hc-BoNT, prevent the destructive effects of neurotoxin complexes. Although toxoid-based botulinum vaccines are safe and effective, their manufacturing process is expensive because it requires large-scale production facilities to handle such high-risk and spore-forming agents. Therefore, current efforts to develop innovative botulinum vaccine strategies have focused on subunit vaccines consisting of HC fragments.
Our Services for Clostridium botulinum Vaccine
- Gene synthesis and cloning
- Expression and purification of the recombinant protein
- Evaluation of the humoral and cellular immune response
With the leading technology and years of experience in vaccines development for the bacterium, Creative Biolabs is able to provide the state-of-art services for any new vaccines with Clostridium botulinum. Our scientists specialized in vaccines studies will work with you to develop a most appropriate strategy that will offer the long-term protection against BoNT. Please don’t hesitate to contact us for more information.
All of our products can only be used for research purposes. These vaccine ingredients CANNOT be used directly on humans or animals.
