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July 17, 2017
By: Mary N. Wessling, Ph.D. ELS
Tetanus Toxin’s Use as a Protein Carrier and Antigen
Tetanus toxin (TT) is the major virulence factor of the Gram-positive bacterium Clostridium tetani. Infection with this bacterium in unvaccinated persons produces muscle spasms by binding to nerve endings and moving throughout the nervous system in a specific way. Eventually, almost total paralysis results. The deactivated toxin is the basis for a vaccine, which can even be administered to pregnant women, usually as part of a combination vaccine also aimed at preventing neonatal pertussis.1 Worldwide, the mortality of infection among unvaccinated persons reaches 10%.2 It is the binding specificity of this dangerous toxin that makes it valuable as a research material. List Biological Laboratories (List Labs) offers inactivated tetanus toxin and six related products, used in intricate and fascinating ways in research as a model antigen and protein carrier.
List Labs’ Tetanus Toxoid in Immunosupression Research
Existing antibody treatments for rheumatic arthritis (RA), for example doses of rituximab every six months, suppress autoreactive B cells by killing them. The effects of the treatment fade over the 6-month period; this increases the inherent risk of infection and progressive multifocal leukoencephalopathy. Chu et al studied a treatment that characterized B-cell immunosuppression by an engineered antibody; List Labs’ tetanus toxoid (TTd) was used in an elegant series of explorations of the mechanism of action of an engineered antibody (XmAb581) that enhanced the action of a B-cell antigen receptor complex currently under clinical development for treatment of RA, and enhanced both its safety and efficacy.3
Tetanus Toxoid in B Cell-Driven Autoimmune Disease Research
In a study with a broader purpose, Klose et al, expanding a previous murine study, developed a protein engineering strategy to selectively target and eradicate human memory B cells. These authors built a fusion protein that combined a model antigen TTd fragment C with a truncated version of exotoxin A derived from Pseudomonas aeruginosa. A fluorescein isocyanate-labelled TT fragment C produced by List Laboratories, used as a control in the binding analysis, played an important supporting role. This research offers a promising approach for the specific depletion of autoreactive B-lymphocytes in B cell-driven autoimmune diseases.4
Prompted by the lower prevalence of these diseases in children who lived near farm animals and in unhygienic environments, Iwasaki et al studied the key role of intestinal infection in development of allergic respiratory disease in children. Their study used List Labs’ TTd antigen These findings support a key role for intestinal infection in the development of allergic respiratory disease.5
Further Innovative Applications of List Labs’ Tetanus Toxin and Tetanus Toxoid
List Labs’ tetanus toxin (TT) Fluorescent images showed that there was a rapid accumulation of Zn2+ in amacrine cell processes after optic nerve injury.6 Investigating yet another problem that affects injured persons, i.e., the necessity to keep an injured limb immobile, which results in muscle atrophy, Matthews et al reported that inactivity can result in 20% to 30% atrophy despite the use of exercise-based or neuromuscular electronic stimulation. They injected either saline or a very dilute solution of List Labs’ TT They found that the TT prevented loss of size in all 3 myofiber types, and therefore was protective against muscle loss during immobility.7
Finally, animal studies are used to evaluate the efficacy of pharmaceutical and other products for human use; although there are stringent conditions that assure ethical treatment of animals, the process is often time-inefficient, inaccurate, and costly. Temann et al explored using precision-cut lung slices (PCLS) from lungs of donors that were not suitable for use in transplantation as an alternative to animal studies. They evaluated a culture system using PCLS stimulated by List Labs’ TTd to study cytotoxic, inflammatory, and immune responses.8
The studies we cite here are only a small sample of what can be accomplished using List Labs’ TT and related products. We invite you to visit our citations page to explore how TT and our other products can augment your experimental design.
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