Monoclonal Antibody Treatment Decreases Severity of Whooping Cough in Animal Models

A pair of antibodies directed against pertussis toxin was shown in animal models to increase bacterial clearance and prevent the rise in white blood cell counts associated with poor prognosis in infants.

Despite widespread vaccination, pertussis rates are rising in industrialized countries and remain high worldwide. With no specific drugs to treat the disease, pertussis continues to cause considerable infant morbidity and mortality. The pertussis toxin, a protein-based AB5-type exotoxin, is a major contributor to the disease state, as it is responsible for local and systemic effects including leukocytosis and immunosuppression.

In an effort to develop means to prevent or treat whooping cough, investigators at the University of Texas (Austin, USA) humanized two mouse monoclonal antibodies that neutralized pertussis toxin. The antibodies were then expressed as human immunoglobulin G1 molecules with no loss of affinity or in vitro neutralization activity. The antibodies were subsequently licensed for further development to Synthetic Biologics (Rockville, MD, USA), a clinical-stage company focused on targeting pathogen-specific diseases.

In a preliminary study the antibodies were administered prophylactically to mice as a binary cocktail and therapeutically to pertussis-infected baboons. Results published in the December 2, 2015, online edition of the journal Science Translational Medicine revealed that in mice the antibody treatment completely mitigated the Bordetella pertussis–induced rise in white blood cell counts and decreased bacterial colonization. When administered therapeutically to baboons, antibody-treated, but not untreated control animals, experienced a blunted rise in white blood cell counts and accelerated bacterial clearance rates.

"In the developing world, an estimated 200,000 babies die a year, and that is where we think we can have a really big impact," said senior author Dr. Jennifer Maynard, associate professor of chemical engineering at the University of Texas. "If we can get our antibodies to these high-risk infants, we could potentially prevent the infection from occurring in the first place. We want to make sure that our research is really going to have impact. Most of the babies who get sick have not been immunized, so we hope to provide the immunity that they are lacking."

"We believe the key to preventing death is reducing the white blood cell load, which becomes extremely elevated during infection," said contributing author Dr. Michael Kaleko, senior vice president of research and development at Synthetic Biologics. "If we can bring the count down or keep it low, the sick child may have a much better prognosis."

Related Links:
University of Texas
Synthetic Biologics