ACELLULAR PERTUSSIS-VACCINE COMPOSED OF GENETICALLY INACTIVATED PERTUSSIS TOXIN

Whooping cough, an acute respiratory disease affecting over sixty mill ion infants, can be prevented by vaccination. The vaccine currently us ed, composed of killed bacterial cells, however, has been associated w ith many side effects. An improved vaccine against the disease should contain pertussis toxin (PT), a major virulent factor of Bordetella pe rtussis (B. pertussis). In order to be included in the vaccine, PT nee ds to be detoxified and the chemical methods used so far are not compl etely satisfactory, since they give a product with reduced immunogenic ity and possible residual toxicity. To avoid this problem, we have use d recombinant DNA technologies to clone the PT gene, express it in bac teria, map the B and T cell epitopes of the molecule and identify the amino acids that are important for the enzymatic activity and toxicity . Based on this information, the gene coding for PT was mutated to pro duce an inactive protein. This genetically modified PT was non toxic, highly immunogenic and able to protect mice from intracerebral challen ge with virulent B. pertussis. The mutant was included as a main compo nent of an acellular pertussis vaccine which has been shown in numerou s clinical trials to be more safe and immunogenic than the old cellula r vaccine.