Toxins as Vaccines and Adjuvants

Abstract

Several bacteria produce potent toxins that are entirely, or in part, responsible for the severe diseases caused by the microorganisms. This chapter describes those toxins classically used to prevent disease and the approaches for their future use. Today, it is possible to inactivate toxins and microorganisms by using genetic tools. Therefore, in addition to traditional diphtheria and tetanus vaccines, the acellular pertussis vaccine is also described in the chapter . This represents the first vaccine produced by genetic inactivation of a bacterial toxin. Several methods have been described for the purification of diphtheria and tetanus toxins and are generally based on diafiltration of culture supernatant, precipitation by ammonium sulfate, and, if necessary, purification by gel filtration or ion-exchange chromatography. With these methods, diphtheria and tetanus toxins can be purified to 85 to 95% purity, representing approximately 2,300 and 1,800-2,000 Lf/mg of protein nitrogen for tetanus and diphtheria, respectively, by ammonium sulfate precipitation, whereas the conventional vaccines have a purity of approximately 60%. Pertussis toxin (PT) plays a central role in the pathogenesis of whooping cough and induces protective immunity against infection. As for the other toxins, to be included in vaccines, PT needs to be detoxified. The most powerful mucosal immunogens and adjuvants recognized to date are cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT). To study the structure-function of CT and LT and to find molecules that are nontoxic but still active as mucosal adjuvants and immunogens, more than 50 site-directed mutations have been generated within these toxins.