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Sci Transl Med. 2015 Dec 2;7(316):316ra195. doi: 10.1126/scitranslmed.aad0966.

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

Author information

1
Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, USA.
2
Department of Veterinary and Biomedical Science, Pennsylvania State University, University Park, PA 16802, USA.
3
Department of Comparative Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
4
The Marine Science Institute, College of Science, University of the Philippines Diliman, Quezon City 1101, Philippines.
5
Synthetic Biologics, 155 Gibbs Street, Suite 412, Rockville, MD 20850, USA.

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.

PMID:
26631634
PMCID:
PMC5075433
DOI:
10.1126/scitranslmed.aad0966
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

M.K. and A.B. are employed by Synthetic Biologics, which has a financial interest in hu1B7 and hu11E6. J.A.M., A.W.N., E.K.W., and E.A.P. have filed a provisional patent jointly with Synthetic Biologics with the US Patent and Trademark Office for humanized pertussis antibodies. This work was supported in part by funding from Synthetic Biologics.

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