Tetanus and diphtheria vaccine response in immunodeficiency diagnostics

Tetanus toxin is a protein produced by Chlostridium tetanii, a bacterium causing tetanus. Corynebacterium diphtheriae, a bacterium causing diphtheria, produces diphtheria toxin. 

The vaccines contain a form of the toxin excreted by the tetanus and diphtheria bacteria rendered harmless, or toxoid. The antibodies produced by vaccination bind to the toxins produced by the bacteria. This prevents toxins from causing tissue damage, for example, in the nervous system or in the myocardium.

When a patient’s symptoms indicate the presence of immunodeficiency, the patient should be examined for antibody concentrations for tetanus and diphtheria toxoids caused by previous vaccinations.

In immunodeficiency diagnostics, the formation of antibodies to tetanus and diphtheria toxoids is used to assess whether the patient has a normal T-dependent B cell response.

Investigating suspected immunodeficiency involves measuring antibodies from serum samples taken before and after vaccination. Measuring the concentration of tetanus and diphtheria antibodies utilises the 2738 S-ClteAb (tetanus) and 1253 S-CodiAb (diphtheria) tests. Responses to a 23 valent pneumococcal polysaccharide vaccine should also always be assessed in immunodeficiency diagnostics.

Instructions for measuring vaccine response

  • Take a serum sample before vaccination and 2–4 weeks after vaccination, but no later than within 2 months.
  • Both tetanus and diphtheria toxoid and pneumococcal polysaccharide antibodies can be measured from the same sample.

Interpretation of tetanus and diphtheria antibody assays

The subject is considered to have sufficient protective antibody levels if the concentration of antibodies measured before vaccination is 

  • ≥ 0,1 IU/ml for tetanus
  • ≥ 0,1 IU/ml for diphtheria

If the subject does not have protective antibody levels for tetanus and diphtheria toxoids, antibody concentrations are also measured from the sample taken after vaccination.

The vaccine response is interpreted as normal if the concentration of antibodies becomes three times higher after vaccination.

The subject is considered to have sufficient antibody levels providing long-term protection if the concentration of antibodies measured after vaccination is

  • ≥ 1 IU/ml for tetanus
  • ≥ 1 IU/ml for diphtheria

A positive antibody concentration providing reliable protection against clinical disease is generally considered to be a concentration greater than or equal to 0.1 IU/ml for both tetanus and diphtheria. A concentration greater than or equal to 1 IU/ml is considered to provide good long-term protection.

In the serum data collected in Finland in 2000-2001, the concentration of antibodies exceeded the concentration of 0.1 IU/ml, the limit value considered to provide sufficient protection, for tetanus in more than 95 per cent and for diphtheria by approximately 80 per cent of adults aged 30–49 [1]. In older age groups, the antibody concentrations of a smaller share of people were at a protective level, especially with regard to diphtheria [1].

The concentration of antibodies to tetanus and diphtheria is estimated to decrease by 10 per cent per year following the vaccination [2]. With the threshold level for protection of 0.1 IU/mL, the post-vaccination antibody concentration should be greater than or equal to 1 IU/mL to maintain the tetanus and diphtheria antibodies at the protective level for the following 20 years [1].

References

1. Ölander RM, Auranen K, Härkänen T, Leino T. High tetanus and diphtheria antitoxin concentrations in Finnish adults – time for new booster recommendations? Vaccine. 2009 Aug 27;27(39):5295–8. 

2. Simonsen O, Badsberg JH, Kjeldsen K, Møller-Madsen B, Heron I. The fall-off in serum concentration of tetanus antitoxin after primary and booster vaccination. Acta Pathol Microbiol Immunol Scand C. 1986 Apr;94(2):77–82.