RATIONAL APPROACHES TO REDUCE ADVERSE REACTIONS IN MAN TO VACCINES CONTAINING TETANUS AND DIPHTHERIA TOXOIDS

Adverse reactions to routine vaccines are obstacles to the mass vaccin ation campaigns. Though the absolute safety of any injectable vaccine cannot be guaranteed, the adverse side effects to vaccines can be mini mized by practicing existing scientific knowledge. Adverse side effect s to tetanus and diphtheria toxoids have been known for many years and there have been ways to minimize these reactions. These procedures di d not get wide acceptance, because the current partially purified teta nus and diphtheria vaccines meet the regulatory requirements and the m anufacturers are reluctant to change the established procedures of pro duction due to the amount of work involved in the regulatory issues un der the current Good Manufacturing Practices (GMP). Due to the recent epidemic of diphtheria in the independent states of the former Soviet Union, and its potential for spread to other. European Countries, vacc ination campaigns with tetanus and diphtheria vaccines received a new boost with several international agencies. In this report, we review t he causes for adverse reactions to tetanus and diphtheria vaccines and offer practical suggestions for minimizing these reactions. The major issues in minimizing adverse reactions to these vaccines include: (1) purifying the toxins before detoxification as the reactogenic accesso ry antigens get covalently bound to the toxins during detoxification; (2) either using well-tolerated adjuvants which do not elicit the prod uction of antigenic specific IgE antibodies responsible for adverse re actions ol by using non-adjuvanted highly immunogenic polymerized anti gens; (3) checking the status of immunity by recently developed rapid serological methods or by the Schick skin-test for diphtheria to avoid allergic or Arthus-type reactions. These approaches are applicable to industrial scales and would result in a pure, less reactogenic and be tter characterized toxoids antigens which would be more suitable for c ombined vaccines comprising highly petrified acellular pertussis compo nents, polysaccharide-protein conjugates and other antigens. (C) 1998 Elsevier Science Ltd. All rights reserved.