title: Mutants of pertussis toxin suitable for vaccine development.
abstract: Immunization with chemically detoxified pertussis toxin can prevent severe whooping cough with an efficacy similar to that of the cellular pertussis vaccine, which normally gives unwanted side effects. To avoid the reversion to toxicity and the loss of immunogenicity that may follow chemical treatment of pertussis toxin, inactive toxins were constructed by genetic manipulation. A number of genetically engineered alleles of the pertussis toxin genes, constructed by replacing either one or two key amino acids within the enzymatically active S1 subunit, were introduced into the chromosome of strains of Bordetella pertussis, B. parapertussis, and B. bronchiseptica. These strains produce mutant pertussis toxin molecules that are nontoxic and immunogenic and that protect mice from the intracerebral challenge with virulent Bordetella pertussis. Such molecules are ideal for the development of new and safer vaccines against whooping cough.
authors.affiliation: Sclavo Research Center, Siena, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pizza
authors.forename: A
authors.initials: A
authors.lastname: Covacci
authors.forename: A
authors.initials: A
authors.lastname: Bartoloni
authors.forename: M
authors.initials: M
authors.lastname: Perugini
authors.forename: L
authors.initials: L
authors.lastname: Nencioni
authors.forename: M T
authors.initials: MT
authors.lastname: De Magistris
authors.forename: L
authors.initials: L
authors.lastname: Villa
authors.forename: D
authors.initials: D
authors.lastname: Nucci
authors.forename: R
authors.initials: R
authors.lastname: Manetti
authors.forename: M
authors.initials: M
authors.lastname: Bugnoli
mesh_terms: D000818:Animals; D005260:Female; D005821:Genetic Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D037342:Pertussis Toxin; D010567:Pertussis Vaccine / Q000633:toxicity*; D011817:Rabbits; D014614:Vaccines, Synthetic / Q000633:toxicity; D010566:Virulence Factors, Bordetella / Q000235:genetics / Q000276:immunology / Q000633:toxicity*
chemical_list: D010567:Pertussis Vaccine; D014614:Vaccines, Synthetic; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin