Protective immunity to Pasteurella multocida heat-labile toxin by intranasal immunization in rabbits

Heat-labile Pasteurella multocida toxin (PMT) is an important virulence factor of some isolates from rabbits. To determine whether protective immunity to PMT could be induced in rabbits by intranasal immunization with heat-inactivated PMT, we immunized groups of rabbits intranasally at days 0, 7, 14, and 21 with inactivated PMT, with or without cholera toxin, an adjuvant for the mucosal immune system. Significant increases in anti-PMT IgA in nasal lavage samples and anti-PMT serum IgG, as determined by enzyme-linked immunosorbent assay, developed within 2 weeks after initial immunization. Coadministration of cholera toxin with inactivated PMT enhanced anti-PMT activity in the samples. Rabbits similarly immunized on days 0, 7, and 14 were challenged with PMT, and tissues were graded histologically on a numeric scale of lesion severity. Immunization conferred partial protection against development of pneumonia, pleuritis, hepatic necrosis, and testicular atrophy in rabbits challenged 16 days after initial immunization. Thus, immunization with inactivated PMT stimulates a protective response to PMT challenge in rabbits that is enhanced by coadministration of cholera toxin.