Chapter 5: Concluding remarks and perspectives

Due to the overall presence of C. tetani in soil and dust, tetanus cannot be eradicated, but only prevented by good hygienic standards and a high vaccination coverage, preferably by properly spaced booster doses of a combined D-T vaccine following a primary vaccination series. The duration of protection acquired by a booster dose of vaccine is influenced by the age at the revaccination and on the dose and the type of the antigen, but it is generally thought to last about 10 years (Simonsen et al., 1987a and 1996). Diphtheria is endemic in parts of the world and the recent epidemic in Eastern Europe have shown that the disease may spread to neighbouring countries affecting susceptible persons with a poor antibody level (Galazka et al., 1995; Galazka & Robertson, 1996; Hardy et al., 1996). This stresses the importance of surveillance studies, especially in connection to changes in vaccination programmes to measure their influence on the herd immunity. Thus, in the present series of studies, a reduced immunity against diphtheria, slightly below the level believed to guard against diphtheria epidemics, was demonstrated among military recruits and ascribed to a change in the vaccination programme from 4 doses of D-T-WP to 3 doses of D-T-IPV given in childhood some 20 years earlier. The one-injection potency assays of D-T vaccines required by Ph. Eur. were proven inadequate in predicting the booster response in man. Consequently, a two-step immunization procedure was suggested introduced, which in combination with serological measurements may give potency results of higher clinical value and with a reduced need for experimental animals. In attempts to eradicate diphtheria, attention was drawn to domestic animals, since the horse in endemic areas may represent a reservoir and a carrier of the disease. This may be verified by an isolation of the bacillus from nasopharyngea1 swaps or perhaps easier by a demonstration of a natural high anti-D antibody level measured directly by the improved Vero cell assay or the developed double-antigen techniques, also suitable for surveillance studies and clinical trials in man. To prevent coupling of foreign proteins including reactogenic material into toxoids, it was shown that toxins should be purified before detoxification with formaldehyde. The optimal DT booster vaccine contains neither adjuvant nor preservative and is applied deep subcutaneously. Such a vaccine was shown to give the lowest frequency of adverse reactions and the strongest antibody response. A reduction of the incidence of adverse reactions may also be accomplished by the use of a carefully chosen dose of calcium phosphate adsorbed D-T vaccine with a similar efficacy in man as the standard aluminium hydroxide adsorbed vaccine. Human studies on the IgG and IgE responses following a primary vaccination series using identical toxoids adsorbed to calcium phosphate or aluminium based adjuvants remain to be conducted. The present trend in vaccine development is to combine more and more antigens in one vaccine dose and to include toxoid carriers in polysaccharide conjugate vaccines in vaccination programmes (Plotkin, 1993; Andrd, 1994; Corbel, 1994; Dittmann, 1994; Hadler, 1994; Gade et al., 1995; Miller, 1996). Unpredictable, mutual interactions between the various antigens may take place: (i) Prior exposure to a toxoid can either enhance or suppress the antibody response to the polysaccharides (Peeters et al., 199 1 ; Barrington et al., 1993).