Toxoid

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Ruby Hirose researching serums and antitoxins Ruby Hirose at the William S. Merrell Laboratories.jpg
Ruby Hirose researching serums and antitoxins
A poster released by the Central Council for Health Education, spreading awareness about Diphtheria. Diphtheria is Deadly Art.IWMPST14182.jpg
A poster released by the Central Council for Health Education, spreading awareness about Diphtheria.
A tetanus vaccine is being administered at the Naval medical Center San Diego US Navy 110827-N-KA543-005 Hospital Corpsman 2nd Class Chris Dunbar, assigned to Naval Medical Center San Diego, gives a patient a tetanus, diphthe.jpg
A tetanus vaccine is being administered at the Naval medical Center San Diego

A toxoid is an inactivated toxin (usually an exotoxin) whose toxicity has been suppressed while retaining its immunogenicity. This is usually achieved by chemical (formalin) or heat treatment. [1] Toxins are secreted by bacteria, whereas toxoids are altered form of toxins; toxoids are not secreted by bacteria. Thus, when used during vaccination, an immune response is mounted and immunological memory is formed against the molecular markers of the toxoid without resulting in toxin-induced illness. Such a preparation is also known as an anatoxin. [2] There are toxoids for prevention of diphtheria, tetanus and botulism. [3]

Contents

Toxoids are used as vaccines because they induce an immune response to the original toxin or increase the response to another antigen since the toxoid markers and toxin markers are preserved. For example, the tetanus toxoid is derived from the tetanospasmin produced by Clostridium tetani . [4] The latter causes tetanus and is vaccinated against by the DTaP vaccine. While patients may sometimes complain of side effects after a vaccine, these are associated with the process of mounting an immune response and clearing the toxoid, not the direct effects of the toxoid. The toxoid does not have virulence as the toxin did before inactivation.

Toxoids are also useful in the production of human antitoxins. Multiple doses of tetanus toxoid are used by many plasma centers in the United States for the development of highly immune persons for the production of human anti-tetanus immune globulin (tetanus immune globulin (TIG), HyperTet (c) [5] ), which has replaced horse serum-type tetanus antitoxin in most of the developed world.

Toxoids are also used in the production of conjugate vaccines. The highly antigenic toxoids help draw attention to weaker antigens such as polysaccharides found in the bacterial capsule. [6]

List of toxoids

ToxinOrganismToxoid
Tetanus toxin Clostridium tetani Tetanus toxoid
Diphtheria toxin Corynebacterium diphtheriae Diphtheria toxoid
Botulinum toxin Clostridium botulinum Botulinum toxoid
Pertussis toxin Bordetella pertussis"Bordetella pertussis toxoid antigen" [7] (see pertussis vaccine)
Tracheal cytotoxin Bordetella pertussis
Erythrogenic toxin Streptococcus pyogenes(PMID 10948118, 10925320)
Leukocidin, Streptolysins Streptococcus pyogenes
Clostridial a-toxin Clostridial perfringens(PMID 4306752)
Cholera toxin Vibrio cholerae [8] (Used in experimental TA-CD)
Anthrax toxin Bacillus anthracis(see anthrax vaccines) [9]
Staphylococcal enterotoxin Staphylococcus aureus(PMID 30824769)
Toxic shock syndrome toxin Staphylococcus aureus(PMID 30824769)
Pseudomonas exotoxin A Pseudomonas aeruginosa(Unnamed; used in Vi-rEPA) [10]

Mechanism of production

Formaldehyde

Formaldehyde seems to inactivate toxins by inducing crosslinking. [11] Overzealous use of formaldehyde can lead to aggregation. [12]

Recombinant

A minority of sources refer to toxins with the dangerous parts genetically edited out and produced using recombinant protein technology as a "recombiant toxoid". [13] [14] Other sources simply call such things a regular recombinant antigen. [15] [16]

References

  1. ↑ Parham, P. (2015). "The Immune System". 4th Ed. Garland Science, Peter & Francis Group, LLC. New York.
  2. ↑ Anatoxin
  3. ↑ Moloney, P. J. (1926). "The Preparation and Testing of Diphtheria Toxoid (Anatoxine-Ramon)". American Journal of Public Health (PDF). 16 (12): 1208–1210. doi:10.2105/AJPH.16.12.1208. PMC   1321494 . PMID   18012024.
  4. ↑ "Diphtheria and Tetanus Toxoids Adsorbed" (PDF). fda.gov. Archived from the original (PDF) on July 10, 2009. Retrieved 21 October 2015.
  5. ↑ "Tetanus Immune Globulin (Human)" (PDF). September 2012. Archived from the original (PDF) on 4 March 2016. Retrieved 2010-05-29.
  6. ↑ Vaccine design : innovative approaches and novel strategies. Rappuoli, Rino., Bagnoli, Fabio. Norfolk, UK: Caister Academic. 2011. ISBN   9781904455745. OCLC   630453151.{{cite book}}: CS1 maint: others (link)
  7. ↑ "Bordetella pertussis toxoid antigen (formaldehyde, glutaraldehyde inactivated)". go.drugbank.com.
  8. ↑ Germanier, R; Fürer, E; Varallyay, S; Inderbitzin, TM (June 1976). "Preparation of a purified antigenic cholera toxoid". Infection and Immunity. 13 (6): 1692–8. doi:10.1128/iai.13.6.1692-1698.1976. PMC   420821 . PMID   823107.
  9. ↑ "NIBSC - Anthrax". www.nibsc.org. It can be prevented by vaccination, and the licensed anthrax vaccine is a toxoid vaccine. It consists of inactivated subunits of anthrax toxin and elicits an antibody response that neutralises anthrax toxin.
  10. ↑ Kossaczka Z, Bystricky S, Bryla DA, Shiloach J, Robbins JB, Szu SC (June 1997). "Synthesis and immunological properties of Vi and di-O-acetyl pectin protein conjugates with adipic acid dihydrazide as the linker". Infection and Immunity. 65 (6): 2088–93. doi: 10.1128/IAI.65.6.2088-2093.1997 . PMC   175288 . PMID   9169736.
  11. ↑ Alsarraf, H; Dedic, E; Bjerrum, MJ; Østergaard, O; Kristensen, MP; Petersen, JW; Jørgensen, R (17 November 2017). "Biophysical comparison of diphtheria and tetanus toxins with the formaldehyde-detoxified toxoids, the main components of diphtheria and tetanus vaccines". Virulence. 8 (8): 1880–1889. doi:10.1080/21505594.2017.1321726. PMID   28430538.
  12. ↑ Long, Z; Wei, C; Ross, R; Luo, X; Ma, X; Qi, Y; Chai, R; Cao, J; Huang, M; Bo, T (1 September 2022). "Effects of detoxification process on toxicity and foreign protein of tetanus toxoid and diphtheria toxoid". Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 1207: 123377. doi:10.1016/j.jchromb.2022.123377. PMID   35905569.{{cite journal}}: CS1 maint: article number as page number (link)
  13. ↑ Moreira, GMSG; Moreira C, Jr; da Cunha, CEP; Mendonça, M; Conceição, FR (2016). "Recombinant Botulinum Toxoids: A Practical Guide for Production". Methods in molecular biology (Clifton, N.J.). 1404: 621–632. doi:10.1007/978-1-4939-3389-1_40. PMID   27076326.
  14. ↑ Oldrini, D; Di Benedetto, R; Carducci, M; De Simone, D; Massai, L; Alfini, R; Galli, B; Brunelli, B; Przedpelski, A; Barbieri, JT; Rossi, O; Giannelli, C; Rappuoli, R; Berti, F; Micoli, F (28 November 2023). "Testing a Recombinant Form of Tetanus Toxoid as a Carrier Protein for Glycoconjugate Vaccines". Vaccines. 11 (12). doi: 10.3390/vaccines11121770 . PMID   38140177.
  15. ↑ Gupta, S; Pellett, S (8 September 2023). "Recent Developments in Vaccine Design: From Live Vaccines to Recombinant Toxin Vaccines". Toxins. 15 (9). doi: 10.3390/toxins15090563 . PMID   37755989.
  16. ↑ Chang, Min-Ju; Ollivault-Shiflett, Morgane; Schuman, Richard; Ngoc Nguyen, Son; Kaltashov, Igor A.; Bobst, Cedric; Rajagopal, Shalini P.; Przedpelski, Amanda; Barbieri, Joseph T.; Lees, Andrew (August 2022). "Genetically detoxified tetanus toxin as a vaccine and conjugate carrier protein". Vaccine. 40 (35): 5103–5113. doi:10.1016/j.vaccine.2022.07.011.
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