Responses to Bordetella pertussis mutant strains and to vaccination in the coughing rat model of pertussis.

Phase I strains 18-323, Tohama and L-84 of Bordetella pertussis produced paroxysmal coughing when encased in agarose beads and administered intrabronchially to adult Sprague-Dawley rats. In contrast, the Phase IV variant of strain L-84 was inactive in cough induction, as was strain BP 357, a transposon-insertion mutant which is deficient only in pertussis toxin (PT). Strain BPM 1809, which lacks only the heat-labile toxin, was similar to the unmodified Phase I strains for cough induction, indicating that this toxin is not needed to induce coughing. B. parapertussis also was inactive as a cough inducer. These results indicate that PT, present in Phase I strains of B. pertussis, and absent from Phase IV strains, strain BP 357 and B. parapertussis, is essential for the induction of paroxysmal coughing in this rat model of whooping cough. Prior injection of DTP (whole-cell) vaccine greatly reduced the incidence of coughing in rats challenged subsequently with Phase I B. pertussis. Serological responses were monitored after intrabronchial infection with the various bacterial strains and after vaccination and challenge. The PT-positive or -negative status of the strains in vivo was confirmed by the appropriate presence or absence of anti-PT IgG in the convalescent sera.