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Dual targeting: Combining costimulation blockade and bortezomib to permit kidney transplantation in sensitized recipients
Figure 1. Animals with dual targeting desensitization show increased level of CMV reactivation, CMV nephritis but antibody against CMV or tetanus were not compromised. Tetanus is a non-communicable neurological disease mediated by a potent exotoxin produced by Clostridium tetani, known as tetanus toxin (TeNT). Clostridium tetani is a strictly anaerobic spore-forming bacillus, with its spores commonly found in warm and moist soil. These spores enter the animal body through open wounds, germinate in anaerobic conditions, and after an incubation period of 3 to 21 days, the tetanus bacilli grow in necrotic tissue, synthesizing and releasing TeNT. TeNT binds to the presynaptic membranes of peripheral motor neurons and sensory neurons, travels retrogradely along axons to the central nervous system, and blocks neurotransmitter release. This leads to the patient's inability to mount any immune response, resulting in symptoms such as muscle spasms, paralysis, lockjaw, and, if untreated, death, with a mortality rate of 100% since the amount of toxin needed to induce an immune response is necessarily lethal. As early as around 3000 BC, there have been records of tetanus symptoms, claiming countless lives over the years. It wasn't until 1890 that TeNT was isolated and confirmed as the culprit behind tetanus symptoms.
Vaccination with a tetanus vaccine, which primarily consists of tetanus toxoid, can stimulate the production of antibodies against tetanus toxin, providing effective prevention of tetanus. Tetanus toxoid is an inactivated form of TeNT. Industrially, Clostridium tetani clinical isolates are fermented in a complex medium, from which TeNT can be extracted from the culture supernatant and then inactivated with formalin to obtain tetanus toxoid. Unlike TeNT, tetanus toxoid is non-toxic but retains its immunogenicity. Despite the ability to produce tetanus vaccine industrially, tetanus remains a significant public health issue. In some developing countries and underdeveloped regions, the vaccination coverage for tetanus among the elderly, pregnant women, and newborns is still insufficient, with little information available on related factors. Therefore, the development of effective tetanus drugs and further investigative studies targeting different populations and countries is crucial.
Currently, in addition to being used in the production of tetanus vaccines, tetanus toxoid is also employed in clinical settings to evaluate vaccine efficacy and safety, to create combination vaccines with other antigens, and as a model antigen to study immune response mechanisms. Furthermore, it is used to delve into the mechanism of action of TeNT and to develop treatments for certain neurological or autoimmune diseases by leveraging its immunomodulatory functions. Notably, tetanus toxoid conjugate vaccines, which combine tetanus toxoid with other antigens (usually polysaccharides), have shown significant activity in preventing various bacterial infections. Examples include pneumococcal conjugate vaccines, Hib vaccines, and meningococcal conjugate vaccines. These vaccines demonstrate greatly enhanced efficacy, especially in children.
Figure 1. Representations of Tetanus Toxin (TeNT) structure and mAbs epitopes (Light chain (active domain): blue, Heavy chain: green (variable domain), pink (binding domain). mAb recognition site: yellow. Overview: Surface representation showing epitope accessibility. Close-up view: Epitope depicted in rod-like form.)(Source: Aliprandini E, et al., 2019)
Clostridium tetani toxoid
Clostridium tetani Tetanus Toxoid protein
C. tetani Tetanus Toxoid protein
Tetanus Toxoid
Inactivated TeNT
References
Q: As I am scientist, I will appreciate more detailed information to toxoid preparation, especially to inactivation, losing of toxicity. I need to know more precisely how molecules I am working with were modified.
A: The Tetanus Toxoid is typically prepared by detoxifying the purified Tetanus Toxin using formaldehyde (formalin) under controlled conditions (concentration, temperature, and pH)
This is the standard pharmacopeial method for converting the toxin into a toxoid.
The molecule loses its neurotoxicity but retains its antigenicity (the ability to trigger an immune response) because the key structural epitopes recognized by the immune system are preserved.
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Tetanus– a case report highlighting the challenges in diagnosis and treatment
Tropical Diseases, Travel Medicine and Vaccines
Authors: Boer, M., de Voogd, M., Niemeijer, N.D. van Hoeven, L.
Animal and human tetanus: An overview on transmission, pathogenesis, epidemiology, diagnosis, and control
Journal of Advances in Microbiology Research
Authors: Pal, M. Rebuma, T. Regassa, M. Tariku, F.
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