Genetically derived toxoids for use as vaccines and adjuvants.
Until very recently, development of vaccines has been based on an empirical approach. For example, bacterial toxins have been detoxified using empirical chemical treatment. Progress in biotechnology and molecular biology has allowed the fine knowledge of the structure-function relationship of several bacterial toxins. Thanks to this, the genetic attenuation of bacterial toxins has been made possible. Following this approach, a genetically detoxified pertussis toxin has been produced. This molecule is now the component of an acellular pertussis vaccine, which has been shown to be highly immunogenic and efficacious in infants. The same strategy of molecular detoxification of bacterial toxins has been applied to cholera toxin and to the Escherichia coli heat-labile enterotoxin. Toxin mutants devoid of any toxic activity have been produced and shown in animals to be highly immunogenic and to exhibit strong adjuvanticity when administered at mucosal sites in conjunction with several antigens. These successful results show that rational design of stronger and safer vaccines is feasible.
Del Giudice
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IRIS Research Center, Chiron SpA, via Fiorentina 1, 53100, Siena, Italy. giuseppe_del_giudice@biocine.it
Rappuoli
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D000276:Adjuvants, Immunologic; D003429:Cross Reactions; D006801:Humans; D009092:Mucous Membrane / Q000276:immunology; D009154:Mutation; D037342:Pertussis Toxin; D013329:Structure-Activity Relationship; D014121:Toxoids / Q000235:genetics*; D010566:Virulence Factors, Bordetella / Q000276:immunology
D000276:Adjuvants, Immunologic; D014121:Toxoids; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin