Research ArticlePERTUSSIS

A cocktail of humanized anti–pertussis toxin antibodies limits disease in murine and baboon models of whooping cough

Science Translational Medicine  02 Dec 2015:
Vol. 7, Issue 316, pp. 316ra195
DOI: 10.1126/scitranslmed.aad0966

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Outsmarting whooping cough to help infants

Whooping cough continues to cause severe illness and death in infants worldwide. Whereas antibiotics are effective in the rare cases when pertussis is diagnosed early, medical interventions are limited and invasive during later stages of the disease. In an effort to help critically ill or at-risk infants, Nguyen et al. developed a cocktail of two humanized antibodies that show promise for halting disease progression. The antibodies both bind to the key virulence factor pertussis toxin at distinct sites, mitigating its damaging effects. In murine and baboon models, antibody treatment increased bacterial clearance and curtailed the rise in white blood cell counts associated with poor prognosis in infants.

Abstract

Despite widespread vaccination, pertussis rates are rising in industrialized countries and remain high worldwide. With no specific therapeutics to treat disease, pertussis continues to cause considerable infant morbidity and mortality. The pertussis toxin is a major contributor to disease, responsible for local and systemic effects including leukocytosis and immunosuppression. We humanized two murine monoclonal antibodies that neutralize pertussis toxin and expressed them as human immunoglobulin G1 molecules with no loss of affinity or in vitro neutralization activity. When administered prophylactically to mice as a binary cocktail, 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. These preliminary findings support further investigation into the use of these antibodies to treat human neonatal pertussis in conjunction with antibiotics and supportive care.

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