Tetanus vaccine

Short description: Vaccines used to prevent tetanus

Tetanus vaccine

Tetanus vaccination is often administered via combination DPT vaccines

Vaccine description
Target disease| Tetanus
Type| Toxoid
Clinical data
MedlinePlus| a682198
License data|

* US DailyMed: Tetanus

Routes of
administration| Injection
ATC code|

* J07AM01 (WHO)

Legal status
Legal status|

* US: ℞-only
* EU: Rx-only [1]

Identifiers
CAS Number|

* 93384-51-1

ChemSpider|

* none

NY (what is this?) (verify)

Tetanus vaccine, also known as tetanus toxoid (TT), is a toxoid vaccine used to prevent tetanus.[2] During childhood, five doses are recommended, with a sixth given during adolescence.[2]

After three doses, almost everyone is initially immune,[2] but additional doses every ten years are recommended to maintain immunity.[3] A booster shot should be given within 48 hours of an injury to people whose immunization is out of date.[4]

Confirming that pregnant women are up to date on tetanus immunization during each pregnancy can prevent both maternal and neonatal tetanus.[2][5][6] The vaccine is very safe, including during pregnancy and in those with HIV/AIDS.[2]

Redness and pain at the site of injection occur in between 25% and 85% of people.[2] Fever, feeling tired, and minor muscle pain occurs in less than 10% of people.[2] Severe allergic reactions occur in fewer than one in 100,000 people.[2]

A number of vaccine combinations include the tetanus vaccine, such as DTaP and Tdap, which contain diphtheria, tetanus, and pertussis vaccines, and DT and Td, which contain diphtheria and tetanus vaccines.[7] DTaP and DT are given to children less than seven years old, while Tdap and Td are given to those seven years old and older.[7][8] The lowercase d and p denote lower strengths of diphtheria and pertussis vaccines.[7]

Tetanus antiserum was developed in 1890, with its protective effects lasting a few weeks.[9][10] The tetanus toxoid vaccine was developed in 1924, and came into common use for soldiers in World War II.[2][11] Its use resulted in a 95% decrease in the rate of tetanus.[2] It is on the World Health Organization's List of Essential Medicines.[12]

## Contents

* 1 Medical uses
* 1.1 Effectiveness
* 1.2 Pregnancy
* 1.3 Specific types
* 1.4 Schedule
* 1.4.1 Additional doses
* 2 Side effects
* 3 Mechanism of action
* 4 History
* 5 Research
* 5.1 Recombinant vaccine
* 6 References
* 7 Further reading
* 8 External links

## Medical uses

### Effectiveness

Decrease in tetanus deaths by age group between 1990 and 2017[13]

Vaccination confers near-complete protection from tetanus, provided the individual has received their recommended booster shots.[14] Globally, deaths from tetanus in newborns decreased from 787,000 in 1988 to 58,000 in 2010, and 34,000 deaths in 2015 (a 96% decrease from 1988).[3][15] In the 1940s, before the vaccine, there were about 550 cases of tetanus per year in the United States, which has decreased to about 30 cases per year in the 2000s.[3] Nearly all cases are among those who have never received a vaccine, or adults who have not stayed up to date on their 10-year booster shots.[16]

### Pregnancy

Guidelines on prenatal care in the United States specify that women should receive a dose of the Tdap vaccine during each pregnancy, preferably between weeks 27 and 36, to allow antibody transfer to the fetus.[5][6] All postpartum women who have not previously received the Tdap vaccine are recommended to get it prior to discharge after delivery.[17] It is recommended for pregnant women who have never received the tetanus vaccine (i.e., neither DTP or DTaP, nor DT as a child or Td or TT as an adult) to receive a series of three Td vaccinations starting during pregnancy to ensure protection against maternal and neonatal tetanus. In such cases, Tdap is recommended to be substituted for one dose of Td, again preferably between 27 and 36 weeks of gestation, and then the series completed with Td.[5][6]

### Specific types

The first vaccine is given in infancy. The baby is injected with the DTaP vaccine, which is three inactive toxins in one injection. DTaP protects against diphtheria, pertussis, and tetanus. This acellular vaccine is safer than the previously used DTP with whole inactivated pertussis (now retroactively notated DTwP[18]).[7] Another option is DT, which is a combination of diphtheria and tetanus vaccines. This is given as an alternative to infants who have conflicts with the DTaP vaccine.[14] Quadrivalent, pentavalent, and hexavalent formulations contain DTaP with one or more of the additional vaccines: inactivated polio virus vaccine (IPV), Haemophilus influenzae type b conjugate, Hepatitis B, with the availability varying in different countries.[19][20][21]

For the every ten-year booster Td or Tdap may be used, though Tdap is more expensive.[6]

### Schedule

Because DTaP and DT are administered to children less than a year old, the recommended location for injection is the anterolateral thigh muscle. However, these vaccines can be injected into the deltoid muscle if necessary.

The World Health Organization (WHO) recommends six doses in childhood starting at six weeks of age.[2] Four doses of DTaP are to be given in early childhood.[14] The first dose should be around two months of age, the second at four months, the third at six, and the fourth from fifteen to eighteen months of age. There is a recommended fifth dose to be administered to four- to six-year-olds.[14]

Td and Tdap are for older children, adolescents, and adults and can be injected into the deltoid muscle.[14] These are boosters and are recommended every ten years. It is safe to have shorter intervals between a single dose of Tdap and a dose of the Td booster.[22]

#### Additional doses

Booster shots are important because lymphocyte production (antibodies) is not at a constant high rate of activity. This is because after the introduction of the vaccine when lymphocyte production is high, the production activity of white blood cells will start to decline. The decline in activity of the T-helper cells means that there must be a booster to help keep the white blood cells active.[23]

Td and Tdap are the booster shots given every ten years to maintain immunity for adults nineteen years of age to sixty-five years of age.[6]

Tdap is given as a one-time, first-time-only dose that includes the tetanus, diphtheria, and acellular pertussis vaccinations.[7] This should not be administered to those who are under the age of eleven or over the age of sixty-five.

Td is the booster shot given to people over the age of seven and includes the tetanus and diphtheria toxoids. However, Td has less of the diphtheria toxoid, which is why the "d" is lowercase and the "T" is capitalized.[7]

In 2020, the US Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) recommended that either tetanus and diphtheria toxoids (Td) vaccine or Tdap to be used for the decennial Td booster, tetanus prevention during wound management, and for additional required doses in the catch-up immunization schedule if a person has received at least one Tdap dose.[6]

## Side effects

A bump resulting from a tetanus vaccine injection

Common side effects of the tetanus vaccine include fever, redness, and swelling with soreness or tenderness around the injection site (one in five people have redness or swelling). Body aches and tiredness have been reported following Tdap. Td / Tdap can cause painful swelling of the entire arm in one of 500 people.[14][24] Tetanus toxoid containing vaccines (DTaP, DTP, Tdap, Td, DT) may cause brachial neuritis at a rate of one out of every 100,000 to 200,000 doses.[3][25]

## Mechanism of action

Vaccination generates artificial active immunity. This type of immunity is generated when a dead or weakened version of the disease enters the body, causing an immune response which includes the production of antibodies. This is beneficial because it means that if the disease is ever introduced into the body, the immune system will recognize the antigen and produce antibodies more rapidly.[26]

In the case of the tetanus toxoid vaccine, the tetanus bacterium Clostridium tetani is grown artificially in a broth. The toxin is harvested from the mass of bacteria and then detoxfied using formaldehyde, forming the toxoid.[27] Formaldehyde prevents the toxin from carrying out its toxic function but still preserve most of the epitopes of the original toxin. As a result, an immune system trained against the toxoid will recognize the real toxin.[28]

## History

The first vaccine for passive immunology was discovered by a group of German scientists under the leadership of Emil von Behring in 1890. The first inactive tetanus toxoid was discovered and produced by the French Gaston Ramon in 1924. A more effective adsorbed version of the vaccine, created in 1938, was proven to be successful when it was used to prevent tetanus in the military during World War II.[14] DTP/DTwP (which is the combined vaccine for diphtheria, tetanus, and pertussis) was first used in 1948, and was continued until 1991, when it was replaced with an acellular form of the pertussis vaccine due to safety concerns.[29] Half of those who received the DT(w)P vaccine had redness, swelling, and pain around the injection site,[14] which convinced researchers to find a replacement vaccine.

Two new vaccines were launched in 1992. These combined tetanus and diphtheria with acellular pertussis (TDaP or DTaP), which could be given to adolescents and adults (as opposed to previously when the vaccine was only given to children).[14]

## Research

### Recombinant vaccine

The production of tetanus toxoid is laborious and prone to potency variation. Recombinant protein technology allows a protein to be mass produced in a transgenic microbe in a more standardized way. A Chinese recombinant tetanus vaccine, which contained the immunogenic Hc domain of the toxin, finished phase 1/2 trial in 2021. The Hc domain is responsible for binding to neuronal cells but cannot elicit damage on its own.[30]

## References

1. ↑ "Active substance: diphtheria / tetanus vaccines (adsorbed), diphtheria vaccines (adsorbed)". List of nationally authorised medicinal products. European Medicines Agency. 14 January 2021. https://www.ema.europa.eu/documents/psusa/diphtheria/tetanus-vaccines-adsorbed-diphtheria-vaccines-adsorbed-list-nationally-authorised-medicinal-products/00001128/202005_en.pdf.
2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 "Tetanus vaccines: WHO position paper – February 2017". Weekly Epidemiological Record 92 (6): 53–76. February 2017. PMID 28185446. https://www.who.int/immunization/policy/position_papers/pp_tetanus_2017_summary.pdf.
3. ↑ 3.0 3.1 3.2 3.3 "Chapter 21: Tetanus". Epidemiology and Prevention of Vaccine-Preventable Diseases (13th ed.). Centers for Disease Control and Prevention (CDC). 2015. https://www.cdc.gov/vaccines/pubs/pinkbook/tetanus.html. This article incorporates text from this source, which is in the public domain.
4. ↑ "Puncture wounds: First aid". 4 February 2015. http://www.mayoclinic.org/first-aid/first-aid-puncture-wounds/basics/art-20056665.
5. ↑ 5.0 5.1 5.2 Centers for Disease Control Prevention (CDC) (February 2013). "Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in pregnant women--Advisory Committee on Immunization Practices (ACIP), 2012". MMWR Morb. Mortal. Wkly. Rep. 62 (7): 131–5. PMID 23425962. PMC 4604886. https://www.cdc.gov/mmwr/pdf/wk/mm6207.pdf. This article incorporates text from this source, which is in the public domain.
6. ↑ 6.0 6.1 6.2 6.3 6.4 6.5 "Use of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccines: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2019". MMWR Morb. Mortal. Wkly. Rep. 69 (3): 77–83. January 2020. doi:10.15585/mmwr.mm6903a5. PMID 31971933. PMC 7367039. https://www.cdc.gov/mmwr/volumes/69/wr/pdfs/mm6903a5-H.pdf. This article incorporates text from this source, which is in the public domain.
7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 "Vaccines: VPD-VAC/Tetanus/main page". Centers for Disease Control and Prevention (CDC). https://www.cdc.gov/vaccines/vpd-vac/tetanus/default.htm. This article incorporates text from this source, which is in the public domain.
8. ↑ "Recommended Child and Adolescent Immunization Schedule for ages 18 years or younger, United States, 2020". 3 February 2020. https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html. This article incorporates text from this source, which is in the public domain.
9. ↑ Evaluating and Standardizing Therapeutic Agents, 1890-1950. Springer. 2010. p. 53. ISBN 978-0-230-28559-0. https://books.google.com/books?id=uuWFDAAAQBAJ&pg=PA53.
10. ↑ Pharmacology for Student and Pupil Nurses and Students in Associated Professions. Elsevier. 2016. p. 162. ISBN 978-1-4831-4131-2. https://books.google.com/books?id=fFl-DAAAQBAJ&pg=PA162.
11. ↑ Introduction to Epidemiology: Distribution and Determinants of Disease. Nelson Education. 2012. p. 251. ISBN 978-1-285-68714-8. https://books.google.com/books?id=U8FuCgAAQBAJ&pg=PA251.
12. ↑ The selection and use of essential medicines, 2025: WHO Model List of Essential Medicines, 24th list. Geneva: World Health Organization. 2025. doi:10.2471/B09474. License: CC BY-NC-SA 3.0 IGO.
13. ↑ "Deaths from tetanus, by age". https://ourworldindata.org/grapher/tetanus-deaths-by-age-group.
14. ↑ 14.0 14.1 14.2 14.3 14.4 14.5 14.6 14.7 14.8 Centers for Disease Control and Prevention (2011). "Tetanus". Epidemiology and Prevention of Vaccine-Preventable Diseases (CDC, Epidemiology and Prevention of Vaccine-Preventable Diseases). Washington, D.C.: Public Health Foundation. ISBN 978-0-01-706609-1. https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/tetanus.pdf. Retrieved 4 January 2016. This article incorporates text from this source, which is in the public domain.
15. ↑ "Tetanus". 9 May 2018. https://www.who.int/news-room/fact-sheets/detail/tetanus.
16. ↑ "About Tetanus". Centers for Disease Control and Prevention (CDC). https://www.cdc.gov/tetanus/about/index.html. This article incorporates text from this source, which is in the public domain.
17. ↑ "Pregnancy Guidelines and Recommendations by Vaccine - Tetanus, Diphtheria, and Pertussis (Tdap); & Tetanus and Diphtheria (Td)". August 2016. https://www.cdc.gov/vaccines/pregnancy/hcp-toolkit/guidelines.html#tdap. This article incorporates text from this source, which is in the public domain.
18. ↑ "Choosing from Whole Cell and Acellular Pertussis Vaccines-Dilemma for the Developing Countries". Iranian Journal of Public Health 46 (2): 272–273. February 2017. PMID 28451568.
19. ↑ "2016 Binational Immunization Resource Tool for Children from Birth Through 18 Years". Centers for Disease Control and Prevention (CDC). https://www.cdc.gov/vaccines/schedules/downloads/child/binational-schedule-pr.pdf. This article incorporates text from this source, which is in the public domain.
20. ↑ Centers for Disease Control Prevention (CDC) (October 2008). "Licensure of a diphtheria and tetanus toxoids and acellular pertussis adsorbed, inactivated poliovirus, and haemophilus B conjugate vaccine and guidance for use in infants and children". MMWR Morb. Mortal. Wkly. Rep. 57 (39): 1079–80. PMID 18830213. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5739a5.htm. Retrieved 22 December 2016. This article incorporates text from this source, which is in the public domain.
21. ↑ "Combined hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type B vaccine; Infanrix™ hexa: twelve years of experience in Italy". Hum Vaccin Immunother 10 (1): 129–37. 2014. doi:10.4161/hv.26269. PMID 24004825.
22. ↑ The Safety of Immunizing with Tetanus–diphtheria–acellular Pertussis Vaccine (Tdap) Less than 2 Years following Previous Tetanus Vaccination: Experience during a Mass Vaccination Campaign of Healthcare Personnel during a Respiratory Illness Outbreak. 2010. pp. 8001–7.
23. ↑ Tetanus: Important New Concepts. Amsterdam: Excerpta Medica. 1981.
24. ↑ "Tdap (Tetanus, Diphtheria, Pertussis) Vaccine Information Statement". August 2021. https://www.cdc.gov/vaccines/hcp/vis/vis-statements/tdap.html. This article incorporates text from this source, which is in the public domain.
25. ↑ "Update: vaccine side effects, adverse reactions, contraindications, and precautions. Recommendations of the Advisory Committee on Immunization Practices (ACIP)". MMWR Recomm Rep 45 (RR-12): 1–35. September 1996. PMID 8801442. https://www.cdc.gov/mmwr/PDF/rr/rr4512.pdf. This article incorporates text from this source, which is in the public domain.
26. ↑ "Vaccines & Immunizations". U.S. Centers for Disease Control and Prevention (CDC). https://www.cdc.gov/vaccines/vac-gen/immunity-types.htm. This article incorporates text from this source, which is in the public domain.
27. ↑ "Package Insert-TENIVAC". https://www.fda.gov/media/76610/download?attachment.
28. ↑ 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.
29. ↑ "Whooping Cough: Vaccine Combined with Tetanus, Diphtheria". https://www.historyofvaccines.org/timeline#EVT_100746.
30. ↑ Xu, X; Yu, R; Xiao, L; Wang, J; Yu, M; Xu, J; Tan, Y; Ma, X et al. (August 2021). "Safety and Immunogenicity of a Recombinant Tetanus Vaccine in Healthy Adults in China: A Randomized, Double-Blind, Dose Escalation, Placebo- and Positive-Controlled, Phase 1/2 Trial.". Advanced science (Weinheim, Baden-Wurttemberg, Germany) 8 (15). doi:10.1002/advs.202002751. PMID 34081408.

## Further reading

* "Prevention of Pertussis, Tetanus, and Diphtheria with Vaccines in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP)". MMWR Recomm Rep 67 (2): 1–44. April 2018. doi:10.15585/mmwr.rr6702a1. ISSN 1057-5987. PMID 29702631. PMC 5919600. https://www.cdc.gov/mmwr/volumes/67/rr/pdfs/rr6702a1-H.pdf.
* "Influenza and Tdap Vaccination Coverage Among Pregnant Women - United States, April 2018". MMWR Morb. Mortal. Wkly. Rep. 67 (38): 1055–1059. September 2018. doi:10.15585/mmwr.mm6738a3. PMID 30260946. PMC 6188122. https://www.cdc.gov/mmwr/volumes/67/wr/pdfs/mm6738a3-H.pdf.
* The immunological basis for immunization series: module 3: tetanus: update 2018. World Health Organization (WHO). 2018. License: CC BY-NC-SA 3.0 IGO. ISBN 978-92-4-151361-6.
* "Chapter 30: Tetanus". Immunisation against infectious disease. Public Health England. 21 January 2021. https://www.gov.uk/government/publications/tetanus-the-green-book-chapter-30.
* "Chapter 21: Tetanus". Epidemiology and Prevention of Vaccine-Preventable Diseases (14th ed.). Washington D.C.: U.S. Centers for Disease Control and Prevention (CDC). 2021. https://www.cdc.gov/vaccines/pubs/pinkbook/tetanus.html.
* "Chapter 16: Tetanus". Manual for the surveillance of vaccine-preventable diseases. Atlanta GA: U.S. Centers for Disease Control and Prevention (CDC). March 2019. https://www.cdc.gov/vaccines/pubs/surv-manual/chpt16-tetanus.html.

## External links

* "Td (Tetanus, Diphtheria) Vaccine Information Statement". August 2021. https://www.cdc.gov/vaccines/hcp/vis/vis-statements/td.html.
* "DTaP (Diphtheria, Tetanus, Pertussis) Vaccine Information Statement". August 2021. https://www.cdc.gov/vaccines/hcp/vis/vis-statements/dtap.html.
* "DTaP/Tdap/Td ACIP Vaccine Recommendations". 28 January 2020. https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/dtap.html.
* Tetanus Toxoid at the US National Library of Medicine Medical Subject Headings (MeSH)
* Diphtheria-Tetanus Vaccine at the US National Library of Medicine Medical Subject Headings (MeSH)
* Diphtheria-Tetanus-Pertussis Vaccine at the US National Library of Medicine Medical Subject Headings (MeSH)
* Diphtheria-Tetanus-acellular Pertussis Vaccines at the US National Library of Medicine Medical Subject Headings (MeSH)

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Artificial induction of immunity / Immunization: Vaccines, Vaccination, Infection, Biology:Inoculat, Inoculation (J07)

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