Background: Pertussis is a significant mortality risk in the developing world, killing up to 200,000 infants annually. Maternal vaccination as a strategy to protect newborns has shown some success, but is unlikely to capture all eligible mothers. Hu1B7 is a monoclonal antibody (mAb) that potently neutralizes pertussis toxin. Hu1B7, when administered as part of a binary mAb cocktail, demonstrated therapeutic efficacy in pertussis-infected weanling baboons. Here, the prophylactic potential of hu1B7 to protect infants during their first few months, when mortality risk is highest, was evaluated.
Methods: Neonatal baboons of normal gestational age (180 days +/- 10), normal birth weight (~1.0 kg), and anti-Fha titer <5 IU/ml (verifying no prior exposure to Bordetella species) were recruited into the study. At 2 days of age, treated baboons received hu1B7 (40 mg/kg, IV), while control animals were untreated. Serum levels of hu1B7 were followed for 5 weeks, at which time the animals were infected with 108 cfu of B. pertussis strain D420. Animals were monitored for clinical signs of disease.
Results: Six controls and 7 treated animals were evaluated. All animals were heavily colonized with B. pertussis during the first week after infection. Controls developed significant leukocytosis, most coughed, and 3 required euthanasia. In contrast, white blood cell counts for all treated animals remained within the normal range, coughing was virtually absent, and all animals maintained normal activity. As expected for a humanized mAb in a non-human primate, hu1B7 had an elimination half-life of 11.8 ± 3.4 days.
Conclusion: Protection of newborn baboons from pertussis was achieved by mAb administration 5 weeks prior to pertussis infection. Hu1B7, when systemically present, mitigated the clinical signs of pertussis, including leukocytosis and coughing, but did not prevent bacterial colonization. Assuming a half-life in humans of 3 weeks, mAb administration at birth could potentially provide 4 months of prophylaxis and is a viable strategy to complement maternal vaccination. Moreover, strategies that extend the mAb half-life and lower the dose could further support developing world application.
Synthetic Biologics, Inc.:
R. Wolf, Synthetic Biologics, Inc.: Collaborator , Research support
J. Papin, Synthetic Biologics, Inc.: Collaborator , Research support
S. Connelly, Synthetic Biologics, Inc.: Employee , Salary
M. Kaleko, Synthetic Biologics, Inc.: Employee and Shareholder , Salary and stock options
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