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

Abstract

Pertussis in infants is often severe, resulting in prolonged hospitalization. Treatment is limited to supportive care. Antibiotics do not significantly alter the course of the disease unless administered during the catarrhal phase. Therapies directed at pertussis toxin, a major virulence factor of Bordetella pertussis, may be beneficial. This study uses the aerosol challenge model to further examine the protective effects of P-IGIV, a new intravenous immunoglobulin product, which has high levels of pertussis toxin antibodies. P-IGIV was prepared as a 4% immunoglobulin G (IgG) solution from the pooled donor plasma from donors immunized with inactivated pertussis toxoid. The IgG pertussis toxin antibody concentration in P-IGIV is >7-fold higher than conventional intravenous immunoglobulin products. In the aerosol challenge model, P-IGIV-treated mice exhibited a dose-dependent decrease in mortality 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 dose of pertussis toxin antibodies in P-IGIV was 147 microg/ml. Recovery of weight gain and normalization of leukocyte counts occurred in all P-IGIV-treated 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 play a role in passive protection but can also reverse symptoms of established disease in mice. We feel that P-IGIV deserves further evaluation in children hospitalized with severe pertussis.

FIG. 1

Pharmacokinetics of human and mouse anti-PT IgG antibodies in BALB/c mice. There was no significant difference (P > 0.05) when the values for volume of distribution and half-life for i.v. administered P-IGIV and i.p. administered P-IGIV were compared. The clearance of mouse anti-PT IgG antibodies was similar to the clearance of human anti-PT IgG antibodies in BALB/c mice. GM, geometric mean. Symbols: , P-IGIV (i.v.); ■, P-IGIV (i.p.); ▴, PHIS (i.p.); and , HuISG (i.p.).