Immunoglobulins
Constantin A. Bona, Francisco A. Bonilla in Textbook of Immunology, 2019
When an antibody binds a virus in such a way that it is no longer infectious, the virus is said to be neutralized, and such an antibody is called neutralizing (discussed further in Chapter 11). The same terminology is used when antibody binding inactivates a toxin. Many bacteria, parasites, plants and animals produce toxins with a variety of deleterious biological effects. One of the most deadly, on a molar basis, is botulinus toxin, a neurotoxin produced by the bacterium Clostridium botulinum. In addition to timely support of vital body functions (such as respiration), injection of a large amount of antibodies binding the toxin (antitoxin, usually prepared in horses) is an important component of therapy. Similarly, when an individual has been bitten or stung by a venomous animal, the appropriate antitoxin may be life-saving. A toxin with which we all (should) have personal experience is the tetanus toxin produced by Clostridium tetanii. Periodically, we (should) be immunized with a formaldehyde-fixed preparation called tetanus toxoid. (An inactivated toxin used for purposes of immunization is called a toxoid.) If immunity to the toxin were not established before infection with C. tetanii, sufficient amounts of neutralizing antibody could not be generated before death.
Neurotoxicology
Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw in Hankey's Clinical Neurology, 2020
Clostridium tetani is a ubiquitous bacterium found in the soil and dust which produces the toxin tetanospasmin, or tetanus toxin, a protein that, like BTX, interferes with neurotransmitter release by impairing vesicle fusion. Unlike BTX, however, tetanospasmin is endocytosed by inhibitory interneurons, where it cleaves the protein synaptobrevin, an essential component of the machinery responsible for vesicle fusion. This leads to an inability of inhibitory interneurons to release GABA and glycine, producing a clinical syndrome of severe uncontrolled muscle contraction, phenotypically similar to strychnine poisoning discussed previously. Given the prevalence of this organism in our environment and the high morbidity and mortality associated with this disease, prevention is critical. Tetanus immunization has become routine throughout the developed world. Once symptoms develop, treatment includes supportive care, including mechanical ventilation if needed, use of BZD and magnesium sulfate to control muscle contractions, antibiotics directed against C. tetani (e.g. metronidazole), and tetanus immune globulin. Initiation of the vaccination series is necessary because contracting tetanus does not confer future immunity.
Surgical infection
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie in Bailey & Love's Short Practice of Surgery, 2018
This is another anaerobic, terminal spore-bearing, grampositive bacterium, which can cause tetanus following implantation into tissues or a wound (which may have been trivial or unrecognised and forgotten). The spores are widespread in soil and manure, and so the infection is more common in traumatic civilian or military wounds. The signs and symptoms of tetanus are mediated by the release of the exotoxin tetanospasmin, which affects myoneural junctions and the motor neurones of the anterior horn of the spinal cord. A short prodromal period, which has a poor prognosis, leads to spasms in the distribution of the short motor nerves of the face followed by the development of severe generalised motor spasms including opsithotonus, respiratory arrest and death. A longer prodromal period of 4-5 weeks is associated with a milder form of the disease. The entry wound may show a localised small area of cellulitis. Exudate or aspirate may give a sample that can be stained to show the presence of gram-positive rods. Prophylaxis with tetanus toxoid is the best preventative treatment but, in an established infection, minor debridement of the wound may need to be performed and antibiotic treatment with benzylpenicillin provided in addition. Relaxants may also be required, and the patient will require ventilation in severe forms, which are associated with a high mortality. The administration of antitoxin using human immunoglobulin ought to be considered for both at-risk wounds and established infection.
Suspected tetanus in an unvaccinated pediatric patient
Published in Baylor University Medical Center Proceedings, 2023
Kimberly Walter, Renita Thomas, Swasti Gyawali, Sowmya Kallur
Tetanus is a life-threatening vaccine-preventable illness. It is caused by tetanospasmin, a potent exotoxin of Clostridium tetani. Tetanospasmin causes neuromuscular dysfunction by inhibiting presynaptic GABA and glycine release. This leads to tonic spasms and paroxysmal contractions of skeletal muscles.1 Spores of Clostridium tetani are present throughout the environment in soil, dust, and manure and are often transmitted to humans via contaminated wounds. Tetanus is extremely rare in the United States due to vaccination efforts, with only 20 cases reported in 2018 and 26 cases in 2019.2,3 Here, we describe a suspected case of tetanus in a 10-year-old unvaccinated child in central Texas resulting in a 1-month stay in the pediatric intensive care unit and ultimately requiring a tracheostomy tube.
Transmission-Blocking Vaccines: Harnessing Herd Immunity for Malaria Elimination
Published in Expert Review of Vaccines, 2021
Patrick E. Duffy
CRM197 and Tetanus Toxoid (TT) have been extensively studied in polysaccharide conjugate vaccines and are used in approved bacterial vaccines [82]. In a recent study, TBV antigens were assessed as immunogens after conjugation to two commercially available CRM197 products: CRM197 expressed in the periplasm of Pseudomonas fluorescens, and EcoCRM® prepared as soluble, intracellular properly folded protein in E. coli [83]. This study also examined TT, as well as a 50 kDa recombinant N-terminal fragment of tetanus toxin heavy chain (rTThc) expressed in E. coli, as carriers for TBV. In mice, Pfs230 conjugates prepared with CRM197, EcoCRM® and TT all induced greater functional activity compared to conjugates prepared with EPA [84].
A vaccine against Alzheimer`s disease: anything left but faith?
Published in Expert Opinion on Biological Therapy, 2019
Martin F. Bachmann, Gary T Jennings, Monique Vogel
Thus, AD vaccines should be optimally designed for the elderly target population to maximize the antibody response by incorporating special adjuvants or delivering extra T-cell help. In addition, using virus-like particles to display Aβ-peptides may be a general way to enhance their immunogenicity [23,29–32]. Indeed, immunization with Aβ-peptides conjugated to VLPs mostly based on bacteriophage Qβ expressed in Escherichia coli [31] or on HPV expressed in plants [32], can induce antibody responses at low doses of antigens and without the use of adjuvant. The VLPs consisting of foreign polypeptides can also serve as a source of T-cell help for Abtea-specific B cells (linked T-cell help), thereby preventing T-cell response against Aβ [33], Furthermore, we have recently shown that incorporation of a universal T-cell epitope derived from tetanus toxin into virus-like particles displaying Aβ1-6 enhances specific IgG responses in old, tetanus-immune mice [34]. This particular vaccine platform combines three important features for the optimal induction of antibody responses (Figure 2). (1) It renders the selected epitope (e.g. Aβ1-6) highly repetitive, enhancing the B cell response [35], (2) The VLPs package bacterial RNA during the assembly process, which serves as a strong adjuvant [36] and drives the induction of IgG subclasses better able to interact with Fc receptors on microglia cells [37], and (3) the incorporation of a universal T-cell epitope derived from tetanus toxin leverages the pre-existing memory Th cells to drive stronger IgG responses.