Immunological studies on tetanus toxoid

T toxoid is one of the most successful vaccines used in immunization programme almost all over the world. Neonatal tetanus can be prevented by immunizing women of childbearing age with tetanus toxoid, either during pregnancy or outside of pregnancy. Tetanus vaccine is used either in mono or in combination with other antigens i.e. Diphtheria, Pertussis (whole cell or acellular), Hepatitis B, Haemophilus influenzae B, Inactivated polio vaccine etc. Tetanus toxoid is produced batch-wise using complex media, often containing poorly defined components. Therefore, batch related quality control to guarantee safety and potency is a statutory requirement. In the new concept, quality control is seen as an instrument to monitor consistency of the critical steps in the production process and testing of vaccines. Monitoring consistency places emphasis on in-vitro methods, since in-vivo tests are less appropriates (expensive, time consuming and inaccurate) for this purpose. Immunochemical techniques may include the use of polyclonal antibodies for direct ELISA or monoclonal antibodies in capture ELISA and immunoblotting to indicate local differences in antigenicity. There is no uniformity in the potency test of tetanus toxoid. Potency assays in animals may be seen as a way of estimating relative antigen contents parallel to the invitro estimations; e.g., by the flocculation tests or the Mancini test. In challenge tests, the ability to create protection against toxin challenge is the reaction used (protective immunogenicity). In antibody production assays the ability to provoke production of antibodies reacting in a certain antibody detection system is used. In the past, the potency of tetanus toxoid was being expressed in Lf units. For the potency estimation of tetanus toxoid component in mono-valent or combination vaccines, the challenge test has been in use for many years. Despite the use of large number of animals (>100 mice or guinea pigs) to test one batch of tetanus toxoid, this test has not been shown to correlate with immunogenicity in humans. However, toxin-neutralizing antibodies induced by the vaccine are generally accepted as correlates of protection. The three ‘R’s concept for the replacement, reduction and refinement of the use of laboratory animal testing is now widely accepted as not only need for ethical but also for scientific reasons.