Tetanus

Our group carries out control testing to ensure the quality and safety of tetanus vaccines and antitoxins, and develops biological standards. This work is underpinned by research that focuses on:

• assay development
• formulation and stability of biological standards
• evaluating novel vaccine antigens, adjuvants and delivery systems

Tetanus is caused by a highly potent neurotoxin produced by Clostridium tetani. The light chain of tetanus toxin is an endopeptidase that cleaves a key component of the intracellular machinery involved in neurotransmitter release. The toxin acts primarily on inhibitory neurons and prevents the release of inhibitory neurotransmitters gamma-aminobutyric acid (GABA) and glycine. This leads to uncontrolled muscle contraction and spasm and produces the classical clinical signs of tetanus.

Vaccination and treatment

Immunity to tetanus can only be induced by immunisation because the amount of toxin needed to cause disease is not enough to stimulate antibody production. The toxin can be chemically inactivated to produce toxoid, and tetanus toxoid is a key component of combined vaccines used in routine immunisation programmes worldwide. The toxoid is adsorbed on to an adjuvant such as aluminium hydroxide or aluminium phosphate to increase antigenicity, and is used alone or in combination with other antigens in combined vaccines.

These combined vaccines contain antigens against diphtheria, pertussis, polio, Haemophilus influenzae type b and hepatitis B virus. Regular booster vaccination with tetanus toxoid is recommended to maintain protective levels of circulating tetanus antitoxin. Purified tetanus-immune globulin (human) is given to people with a tetanus-prone wound who do not have a full history of tetanus vaccination.

Standardisation

NIBSC is responsible for developing, producing and characterising biological reference materials used for standardising tetanus vaccines, antitoxins and related products or intermediates. We maintain a portfolio of tetanus standards, including toxoids and antitoxins, that are used to standardise:

• vaccine and antitoxin potency tests
• assays to measure tetanus antigen content and purity
• serological assays for titration of immune sera

We design and coordinate international collaborative studies to characterise and calibrate new and replacement International Standards. We also work closely with formulation scientists at NIBSC to optimise formulations to successfully freeze-dry tetanus standards.

Control testing

NIBSC carries out scientific testing for tetanus vaccines as part of its role as a National Control Laboratory. We also perform testing for the World Health Organisation (WHO) Prequalification Programme for vaccines. We have wide experience in testing tetanus vaccines, antitoxins and related intermediates and can perform assays for:

• vaccine potency (challenge and serological models)
• antitoxin potency (toxin neutralisation test, ELISA)
• identity (immunodiffusion and ELISA methods)
• antigen content and degree of adsorption (ELISA)
• toxicity

Research and development

We have wide experience in developing and validating methods used to control and standardise tetanus vaccines, antitoxins and related intermediates. We focus firmly on methods that can be used to refine, reduce or replace animal testing – known as the 3Rs –  and have developed and validated an in vitro assay to monitor consistent production of tetanus vaccines.

We worked closely with the European Directorate for the Quality of Medicines and Healthcare (EDQM) and the European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) on an international collaborative study to validate a modified potency test for tetanus vaccine based on using a serological model to replace the direct challenge model. Other research areas include novel tetanus antigens and delivery systems, and we are currently working on developing a cell-based assay for tetanus toxin.

Our scientists collaborate with many UK, European and Global expert groups as part of different grant-funded consortia, currently including: 
VAC2VAC – a wide-ranging collaborative research project funded by IMI2 which aims to develop and validate quality testing approaches for both human and veterinary vaccines using non-animal methods.

Contact us by emailing email bacvac@mhra.gov.uk for information about control testing, standardisation or potential research collaboration.