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

人源化抗百日咳毒素抗体混合物可限制小鼠和狒狒百日咳模型中的疾病

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作者:Annalee W Nguyen, Ellen K Wagner, Joshua R Laber, Laura L Goodfield, William E Smallridge, Eric T Harvill, James F Papin, Roman F Wolf, Eduardo A Padlan, Andy Bristol, Michael Kaleko, Jennifer A Maynard

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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