A cocktail of humanized anti–pertussis toxin antibodies limits disease in murine and baboon models of whooping cough
Autor: | Eduardo A. Padlan, Michael Kaleko, Eric T. Harvill, Jennifer A. Maynard, Joshua R. Laber, William E. Smallridge, Laura L. Goodfield, James F. Papin, Roman F. Wolf, Andy Bristol, Ellen K. Wagner, Annalee W. Nguyen |
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Rok vydání: | 2015 |
Předmět: |
Bordetella pertussis
Whooping Cough medicine.drug_class Immunoglobulin Variable Region Enzyme-Linked Immunosorbent Assay CHO Cells Antibodies Monoclonal Humanized Pertussis toxin Monoclonal antibody Article Mice Cricetulus Neutralization Tests White blood cell medicine Animals Humans Leukocytosis Whooping cough Mice Inbred BALB C biology business.industry Vaccination Infant General Medicine Prognosis biology.organism_classification medicine.disease medicine.anatomical_structure Pertussis Toxin Immunoglobulin G Immunology Disease Progression biology.protein Antibody medicine.symptom business Papio |
Zdroj: | Science Translational Medicine. 7 |
ISSN: | 1946-6242 1946-6234 |
Popis: | 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. |
Databáze: | OpenAIRE |
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