Whooping cough is caused by an infection of the respiratory tract with Bordetella pertussis bacteria. This disease is effectively controlled by the current vaccine which consists of killed whole B. pertussis cells. Though efficacious, the present vaccine produces unacceptable side effects. The major protective antigen in whooping cough vaccines is pertussis toxin. Clinical trials of acellular pertussis products strongly indicate that pertussis toxin will be a necessary and perhaps sufficient component of any new vaccine. Chemically """"""""inactivated"""""""" pertussis toxin vaccines have been produced with reduced side effects and reasonable efficacy, however, residual activity may exist. Using site-specific DNA mutagenesis, we modified an E. coli subclone of the pertussis toxin S1 subunit and then used these constructs to replace the chromosomal copy of the toxin gene in B. pertussis strain 3779. The resulting new strain produces a fully genetically detoxified form of pertussis toxin which is strongly immunoprotective and can be used as a vaccine antigen without chemical inactivation. Molecular studies are currently underway in our laboratory to develop high yield B. pertussis strains to enhance expression of pertussis toxin for use in acellular and conjugate vaccine manuacture.
