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Protective effects of pertussis immunoglobulin (P-IGIV) in the aerosol challenge model
1Dana Farber Cancer Institute and Harvard University Medical School, Boston, Massachusetts 02115, USA. jbbruss@am.pnu.com
Insights
New intravenous immunoglobulin (P-IGIV) with high pertussis toxin antibody levels significantly reduced mortality in a mouse model of pertussis. P-IGIV even reversed established disease symptoms, suggesting potential therapeutic benefits for severe infant pertussis.
Area of Science:
- Immunology
- Infectious Diseases
- Pediatrics
Background:
- Pertussis (whooping cough) in infants often leads to severe illness and prolonged hospitalization.
- Current treatments are primarily supportive, as antibiotics are only effective in the early catarrhal phase.
- Pertussis toxin is a key virulence factor, suggesting targeted therapies may be beneficial.
Purpose of the Study:
- To evaluate the protective efficacy of P-IGIV, a novel intravenous immunoglobulin (IVIG) product with elevated pertussis toxin antibodies.
- To investigate the potential of P-IGIV to mitigate disease severity and mortality in a mouse model of pertussis.
Main Methods:
- Aerosol challenge model in mice using Bordetella pertussis.
- Administration of P-IGIV at varying doses (2,800, 1,400, and 350 mg/kg) compared to saline and conventional human IVIG.
- Monitoring mortality, weight gain, and leukocyte counts for 28 days post-infection.
Main Results:
- P-IGIV demonstrated a dose-dependent reduction in mortality, significantly protecting mice compared to controls.
- The 50% protective dose (PD50) for pertussis toxin antibodies in P-IGIV was determined to be 147 µg/mL.
- Weight recovery and leukocyte normalization were observed in P-IGIV treated groups, with effects seen even when treatment was initiated 7 days post-infection.
Conclusions:
- Pertussis toxin antibodies in P-IGIV provide passive protection and can reverse established pertussis symptoms in a mouse model.
- P-IGIV shows promise as a potential therapeutic agent for severe pertussis in infants.
- Further clinical evaluation of P-IGIV in hospitalized children with severe pertussis is warranted.
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.