{{Short description|Weakened form of a toxin, often used for vaccines}} {{More citations needed|date=December 2009}} [[File:Ruby Hirose at the William S. Merrell Laboratories.jpg|thumb|Ruby Hirose researching serums and antitoxins]] thumb|A poster released by the Central Council for Health Education, spreading awareness about Diphtheria. thumb|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.<ref>Parham, P. (2015). "The Immune System". 4th Ed. Garland Science, Peter & Francis Group, LLC. New York.</ref> 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'''.<ref>[https://www.vocabulary.com/dictionary/anatoxin Anatoxin]</ref> There are toxoids for prevention of diphtheria, tetanus and botulism.<ref>{{cite journal|title=The Preparation and Testing of Diphtheria Toxoid (Anatoxine-Ramon)|type=PDF|journal=American Journal of Public Health|year=1926 |doi=10.2105/AJPH.16.12.1208 |last1=Moloney |first1=P. J. |volume=16 |issue=12 |pages=1208–1210 |pmid=18012024 |pmc=1321494 }}</ref>
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''.<ref>{{cite web|url=https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM142732.pdf |archive-url=https://web.archive.org/web/20090710171316/http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM142732.pdf |archive-date=July 10, 2009 |title=Diphtheria and Tetanus Toxoids Adsorbed|work=fda.gov|access-date=21 October 2015}}</ref> 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)<ref>{{cite web|archive-url=https://web.archive.org/web/20160304091829/http://www.talecris-pi.info/inserts/hypertet.pdf|archive-date=4 March 2016|url=http://www.talecris-pi.info/inserts/hypertet.pdf|title=Tetanus Immune Globulin (Human)|access-date=2010-05-29|date=September 2012}}</ref>), 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.<ref>{{Cite book|title=Vaccine design: innovative approaches and novel strategies|date=2011|publisher=Caister Academic|others=Rappuoli, Rino., Bagnoli, Fabio.|isbn=978-1-904455-74-5|location=Norfolk, UK|oclc=630453151}}</ref>
== List of toxoids == {{incomplete list|date=December 2020}} {|class=wikitable !Toxin !! Organism !! Toxoid |- |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"<ref>{{cite web |title=Bordetella pertussis toxoid antigen (formaldehyde, glutaraldehyde inactivated) |url=https://go.drugbank.com/drugs/DB10991 |website=go.drugbank.com}}</ref> (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'' || <ref>{{cite journal |last1=Germanier |first1=R |last2=Fürer |first2=E |last3=Varallyay |first3=S |last4=Inderbitzin |first4=TM |title=Preparation of a purified antigenic cholera toxoid. |journal=Infection and Immunity |date=June 1976 |volume=13 |issue=6 |pages=1692–8 |doi=10.1128/iai.13.6.1692-1698.1976 |pmid=823107 |pmc=420821}}</ref>(Used in experimental TA-CD) |- |Anthrax toxin || ''Bacillus anthracis'' || (see anthrax vaccines)<ref>{{cite web |title=NIBSC - Anthrax |url=https://www.nibsc.org/science_and_research/bacteriology/anthrax.aspx |website=www.nibsc.org |quote=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.}}</ref> |- |Staphylococcal enterotoxin || ''Staphylococcus aureus'' || (PMID 30824769) |- |Toxic shock syndrome toxin || ''Staphylococcus aureus'' || (PMID 30824769) |- |''Pseudomonas'' exotoxin A || ''Pseudomonas aeruginosa'' || (Unnamed; used in Vi-rEPA)<ref>{{cite journal | vauthors = Kossaczka Z, Bystricky S, Bryla DA, Shiloach J, Robbins JB, Szu SC | title = Synthesis and immunological properties of Vi and di-O-acetyl pectin protein conjugates with adipic acid dihydrazide as the linker | journal = Infection and Immunity | volume = 65 | issue = 6 | pages = 2088–93 | date = June 1997 | pmid = 9169736 | doi = 10.1128/IAI.65.6.2088-2093.1997 | pmc = 175288 | doi-access = free }}</ref> |}
== Mechanism of production ==
=== Formaldehyde === Formaldehyde seems to inactivate toxins by inducing crosslinking.<ref>{{cite journal |last1=Alsarraf |first1=H |last2=Dedic |first2=E |last3=Bjerrum |first3=MJ |last4=Østergaard |first4=O |last5=Kristensen |first5=MP |last6=Petersen |first6=JW |last7=Jørgensen |first7=R |title=Biophysical comparison of diphtheria and tetanus toxins with the formaldehyde-detoxified toxoids, the main components of diphtheria and tetanus vaccines. |journal=Virulence |date=17 November 2017 |volume=8 |issue=8 |pages=1880–1889 |doi=10.1080/21505594.2017.1321726 |pmid=28430538 |pmc=5810461 }}</ref> Overzealous use of formaldehyde can lead to aggregation.<ref>{{cite journal |last1=Long |first1=Z |last2=Wei |first2=C |last3=Ross |first3=R |last4=Luo |first4=X |last5=Ma |first5=X |last6=Qi |first6=Y |last7=Chai |first7=R |last8=Cao |first8=J |last9=Huang |first9=M |last10=Bo |first10=T |title=Effects of detoxification process on toxicity and foreign protein of tetanus toxoid and diphtheria toxoid. |journal=Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences |date=1 September 2022 |volume=1207 |article-number=123377 |doi=10.1016/j.jchromb.2022.123377 |pmid=35905569}}</ref>
=== 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".<ref>{{cite book |last1=Moreira |first1=GMSG |last2=Moreira C |first2=Jr |last3=da Cunha |first3=CEP |last4=Mendonça |first4=M |last5=Conceição |first5=FR |chapter=Recombinant Botulinum Toxoids: A Practical Guide for Production |title=Vaccine Design |series=Methods in Molecular Biology (Clifton, N.J.) |date=2016 |volume=1404 |pages=621–632 |doi=10.1007/978-1-4939-3389-1_40 |pmid=27076326 |isbn=978-1-4939-3388-4 }}</ref><ref>{{cite journal |last1=Oldrini |first1=D |last2=Di Benedetto |first2=R |last3=Carducci |first3=M |last4=De Simone |first4=D |last5=Massai |first5=L |last6=Alfini |first6=R |last7=Galli |first7=B |last8=Brunelli |first8=B |last9=Przedpelski |first9=A |last10=Barbieri |first10=JT |last11=Rossi |first11=O |last12=Giannelli |first12=C |last13=Rappuoli |first13=R |last14=Berti |first14=F |last15=Micoli |first15=F |title=Testing a Recombinant Form of Tetanus Toxoid as a Carrier Protein for Glycoconjugate Vaccines. |journal=Vaccines |date=28 November 2023 |volume=11 |issue=12 |page=1770 |doi=10.3390/vaccines11121770 |doi-access=free|pmid=38140177 |pmc=10747096 }}</ref> Other sources simply call such things a regular recombinant antigen.<ref>{{cite journal |last1=Gupta |first1=S |last2=Pellett |first2=S |title=Recent Developments in Vaccine Design: From Live Vaccines to Recombinant Toxin Vaccines. |journal=Toxins |date=8 September 2023 |volume=15 |issue=9 |page=563 |doi=10.3390/toxins15090563 |doi-access=free|pmid=37755989 |pmc=10536331 }}</ref><ref>{{cite journal |last1=Chang |first1=Min-Ju |last2=Ollivault-Shiflett |first2=Morgane |last3=Schuman |first3=Richard |last4=Ngoc Nguyen |first4=Son |last5=Kaltashov |first5=Igor A. |last6=Bobst |first6=Cedric |last7=Rajagopal |first7=Shalini P. |last8=Przedpelski |first8=Amanda |last9=Barbieri |first9=Joseph T. |last10=Lees |first10=Andrew |title=Genetically detoxified tetanus toxin as a vaccine and conjugate carrier protein |journal=Vaccine |date=August 2022 |volume=40 |issue=35 |pages=5103–5113 |doi=10.1016/j.vaccine.2022.07.011|doi-access=free |pmid=35871872 |pmc=10336728 }}</ref>
== References == {{Reflist|colwidth=30em}}
{{Vaccines}}
Category:Immunology {{Vaccine-stub}}