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)
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Authors | R Rappuoli, A Podda, M Pizza, A Covacci, A Bartoloni, M T de Magistris, L Nencioni |
Journal | Vaccine
(Vaccine)
Vol. 10
Issue 14
Pg. 1027-32
( 1992)
ISSN: 0264-410X [Print] Netherlands |
PMID | 1471424
(Publication Type: Journal Article, Review)
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Chemical References |
- Pertussis Vaccine
- Recombinant Proteins
- Vaccines, Synthetic
- Virulence Factors, Bordetella
- Pertussis Toxin
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Topics |
- Animals
- Bordetella pertussis
(immunology)
- Child
- Child, Preschool
- Clinical Trials as Topic
- Guinea Pigs
- Humans
- Incidence
- Infant
- Mice
- Pertussis Toxin
- Pertussis Vaccine
(adverse effects, immunology)
- Recombinant Proteins
(immunology)
- United States
(epidemiology)
- Vaccination
(adverse effects)
- Vaccines, Synthetic
- Virulence Factors, Bordetella
(chemistry, genetics, immunology, toxicity)
- Whooping Cough
(epidemiology, prevention & control)
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