title: Progress towards the development of new vaccines against whooping cough.
abstract: Acellular vaccines against whooping cough are in the final stage of clinical testing and are likely to become available for mass immunization in the near future. Over a dozen vaccines of similar composition have been developed by vaccine companies and research laboratories; all of them contain a detoxified form of pertussis toxin (PT) that may be present alone or combined with one or more other non-toxic proteins, such as filamentous haemagglutinin (FHA), pertactin (69 kDa), and the agglutinogens (AGG). Most of the vaccines contain a PT that has been inactivated by chemical treatment, a process that reduces the immunogenicity of the molecule and may not completely eliminate the risk of reversion to toxicity. To avoid these problems, we have constructed by genetic manipulation a mutant of Bordetella pertussis that produces a non-toxic form of PT. This molecule (PT-9K/129G) contains two amino acid substitutions in the S1 subunit (Arg9-->Lys and Glu129-->Gly) which abolish the enzymatic activity of the S1 subunit and all the toxic properties of PT, without changing the immunological properties of the wild-type toxin. Following extensive preclinical studies, which have shown that PT-9K/129G is safe and more antigenic than the toxin treated with chemical agents, this molecule was tested for safety and immunogenicity in adult volunteers, 18-month-old children and 2-month-old infants. The molecule has been tested alone, combined with FHA and pertactin and also combined with diphtheria and tetanus toxoids.(ABSTRACT TRUNCATED AT 250 WORDS)
authors: Immunobiology Research Institute, Siena, Italy.
authors: R
authors: R
authors: Rappuoli
authors: A
authors: A
authors: Podda
authors: M
authors: M
authors: Pizza
authors: A
authors: A
authors: Covacci
authors: A
authors: A
authors: Bartoloni
authors: M T
authors: MT
authors: de Magistris
authors: L
authors: L
authors: Nencioni
mesh_terms: D000818:Animals; D001886:Bordetella pertussis / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D006168:Guinea Pigs; D006801:Humans; D015994:Incidence; D007223:Infant; D051379:Mice; D037342:Pertussis Toxin; D010567:Pertussis Vaccine / Q000009:adverse effects / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D014481:United States / Q000453:epidemiology; D014611:Vaccination / Q000009:adverse effects; D014614:Vaccines, Synthetic; D010566:Virulence Factors, Bordetella / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000633:toxicity; D014917:Whooping Cough / Q000453:epidemiology / Q000517:prevention & control*
chemical_list: D010567:Pertussis Vaccine; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin