title: A cocktail of humanized anti-pertussis toxin antibodies limits disease in murine and baboon models of whooping cough.
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.
authors.affiliation: Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Annalee W
authors.initials: AW
authors.lastname: Nguyen
authors.affiliation: Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Ellen K
authors.initials: EK
authors.lastname: Wagner
authors.affiliation: Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Laber
authors.affiliation: Department of Veterinary and Biomedical Science, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Goodfield
authors.affiliation: Department of Veterinary and Biomedical Science, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Smallridge
authors.affiliation: Department of Veterinary and Biomedical Science, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Harvill
authors.affiliation: Department of Comparative Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Papin
authors.affiliation: Department of Comparative Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Roman F
authors.initials: RF
authors.lastname: Wolf
authors.affiliation: The Marine Science Institute, College of Science, University of the Philippines Diliman, Quezon City 1101, Philippines.
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Padlan
authors.affiliation: Synthetic Biologics, 155 Gibbs Street, Suite 412, Rockville, MD 20850, USA.
authors.forename: Andy
authors.initials: A
authors.lastname: Bristol
authors.affiliation: Synthetic Biologics, 155 Gibbs Street, Suite 412, Rockville, MD 20850, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Kaleko
authors.affiliation: Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Maynard
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry*; D001886:Bordetella pertussis; D016466:CHO Cells; D003412:Cricetulus; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007135:Immunoglobulin Variable Region; D007223:Infant; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D010215:Papio; D037342:Pertussis Toxin / Q000737:chemistry*; D011379:Prognosis; D014611:Vaccination; D014917:Whooping Cough / Q000628:therapy*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D037342:Pertussis Toxin