Protective effects of pertussis immunoglobulin (P-IGIV) in the aerosol challenge model

Pertussis in infants is often severe, resulting in prolonged hospitalizatio n. Treatment is limited to supportive care. Antibiotics do not significantl y alter the course of the disease unless administered during the catarrhal phase. Therapies directed at pertussis toxin, a major virulence factor of B ordetella pertussis, may be beneficial. This study uses the aerosol challen ge model to further examine the protective effects of P-IGIV, a new intrave nous immunoglobulin product, which has high levels of pertussis toxin antib odies. P-IGIV was prepared as a 4% immunoglobulin G (IgG) solution from the pooled donor plasma from donors immunized with inactivated pertussis toroi d. The IgG pertussis toxin antibody concentration in P-IGIV is >7 fold high er than conventional intravenous immunoglobulin products. In the aerosol ch allenge model, P-IGIV-treated mice exhibited a dose-dependent decrease in m ortality when monitored for 28 days postchallenge. P-IGIV in doses of 2,800 , 1,400, and 350 mg/kg significantly reduced mortality compared to saline ( P < 0.01)- and human IGIV (P < 0.01)-treated controls. The 50% protective d ose of pertussis toxin antibodies in P-IGIV was 147 mu g/ml. Recovery of we ight gain and normalization of leukocyte counts occurred in all P-IGIV-trea ted groups but did not exhibit dose-dependent characteristics. Even after 7 days of infection, P-IGIV reversed the effects of pertussis in mice. This study provides further evidence that pertussis toxin antibodies not only pl ay a role in passive protection but can also reverse symptoms of establishe d disease in mice. We feel that P-IGIV deserves further evaluation in child ren hospitalized with severe pertussis.