title: Recombinant acellular pertussis vaccine--from the laboratory to the clinic: improving the quality of the immune response.
abstract: Vaccination is the most effective way to prevent infectious diseases. Recombinant DNA technologies have provided powerful new tools to develop vaccines that were previously impossible or difficult to make, and to improve the vaccines that were already available but had been developed using old technology. In the case of whooping cough, an effective vaccine (composed of killed bacterial cells) is available, but its use is controversial because of the many side effects that have been associated with it. An improved vaccine against this disease should contain pertussis toxin, a molecule that needs to be detoxified in order to be included in the vaccine. Classical methods of detoxification, such as formaldehyde treatment have been used to inactivate this toxin. We have used recombinant DNA technologies to clone the pertussis toxin gene, express it in bacteria, map the B and T cell epitopes of the molecule, and to identify the amino acids that are important for enzymatic activity and toxicity. Finally, we have used this information to mutate the gene in the chromosome of Bordetella pertussis in order to obtain a strain that produces a molecule that is already non-toxic. This genetically inactivated pertussis toxin was tested extensively in animal models and clinical trials and was found to induce an immune response that is superior in quality and quantity to that induced by the vaccines produced by conventional technologies.
authors.affiliation: Immunobiology Research Institute Siena, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Rappuoli
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: L
authors.initials: L
authors.lastname: Nencioni
authors.forename: A
authors.initials: A
authors.lastname: Podda
authors.forename: M T
authors.initials: MT
authors.lastname: De Magistris
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001886:Bordetella pertussis / Q000276:immunology; D003001:Cloning, Molecular; D006224:Cricetinae; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D037342:Pertussis Toxin; D010567:Pertussis Vaccine / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology; D010566:Virulence Factors, Bordetella / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000633:toxicity; D014917:Whooping Cough / Q000517:prevention & control*
chemical_list: D000939:Epitopes; D010567:Pertussis Vaccine; D014614:Vaccines, Synthetic; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin