Toxoid vaccines are a subgroup of dead vaccines . They contain toxoids as an effective ingredient and are used in active vaccinations . Toxoids are detoxified toxins in which the properties responsible for toxicity have been destroyed by special processes, whereby the antigenic effect is retained, i.e. the immune system is stimulated to produce antibodies against the toxin. Toxoid vaccines are widely used in the prophylaxis of diphtheria ( diphtheria vaccine ) and tetanus ( tetanus vaccine ).
The production of toxoid vaccines begins with a bacterial culture of the pathogenic bacteria Clostridium tetani or Corynebacterium diphtheriae . These bacteria produce exotoxins that are released into the nutrient medium. These toxins are obtained by sterile filtration and treated with formaldehyde solution for several days at 30–40 ° C for detoxification . Under these conditions, free amino groups in the protein side chains of the toxins react with formaldehyde to form azomethine groups. This modification has the effect that, for example, tetanospasmin can no longer bind to gangliosides and thus has lost its toxic effect. Instead of inactivation with fixatives such as formaldehyde, detoxification can also take place in the course of a protein design.
Purification and formulation
The raw toxoid produced in this way is processed into a highly pure toxoid using standard protein purification methods . Among other things, the harmful formaldehyde is removed; the pharmacopoeia regulations require less than 0.02% formaldehyde in the vaccine. The purified toxoid must also be checked for the presence of undesirable toxoid dimers or polymers; these do not induce immunity to the toxin.
Before being released, each newly manufactured batch of a toxoid vaccine must be tested for effectiveness and harmlessness in animal experiments . House guinea pigs are usually used, which should be immune to the administration of a dose of the toxic toxin after vaccination. In addition, the animals must not show any specific toxicity even after an overdose of the vaccine; In the case of vaccination with tetanus toxoid vaccine, the animals must show no signs of tetanus disease within six weeks.
Toxoid vaccines are rarely used as individual vaccines. Tetanus toxoid vaccine (Tetanol ® ) is occasionally used for simultaneous vaccination with tetanus immunoglobulin if the vaccination protection is unclear or not available in the case of injured persons, but diphtheria and tetanus combination vaccines (Td) are also administered in these cases. Standard are the Td combination vaccines for booster vaccinations in adults; this should be done every ten years. Possibly. In combination, a refresher against whooping cough (TdP) should also be carried out. For primary immunization in infants and children according to the vaccination calendar , other combination vaccines such as the DTP vaccine or a hexavalent vaccine are preferably used. Toxoid vaccines are well tolerated and can also be used in pregnant women, for example. The most common side effects are pain, swelling and hardening at the injection site, and muscle pain.
Toxoids were described by Paul Ehrlich in the late 1890s . The first toxoid vaccines were tested on horses from 1904, both by Ernst Löwenstein and Alexander Glenny . The toxoid vaccines (also called anatoxins) were formaldehyde- and heat-inactivated diphtheria vaccines and were developed from 1923 by the French veterinarian Gaston Ramon at the Pasteur Institute . From 1931 aluminum salts were used as adjuvants for toxoid vaccines. The toxoid vaccines according to Ramon are thus the oldest vaccines that are routinely used today.
- Sara Cohen: Novel Strategies in the Design and Production of Vaccines. Springer Science & Business Media, 2013, ISBN 978-1-489-91382-1 , p. 74.
- Bundesgesundheitsbl 2009 . In: PEI . 2009. Archived from the original on October 31, 2014. Info: The archive link was automatically inserted and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Retrieved January 2, 2016.
- Andrew W. Artenstein: Vaccines: A Biography. Springer Science & Business Media, 2009, ISBN 978-1-441-91108-7 , p. 113 ( limited preview in Google book search).
- Ernst Maschmann, Emil Küster, Werner Fischer: About the ability of clay preparation B to adsorb diphtheria toxin. In: Reports of the German Chemical Society. 64, 1931, p. 2174, doi : 10.1002 / cber.19310640851 .