@article{7b45ea3857464c6cae4057903c3c60a1,
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.",
author = "Nguyen, {Annalee W.} and Wagner, {Ellen K.} and Laber, {Joshua R.} and Goodfield, {Laura L.} and Smallridge, {William E.} and Harvill, {Eric T.} and Papin, {James F.} and Wolf, {Roman F.} and Padlan, {Eduardo A.} and Andy Bristol and Michael Kaleko and Maynard, {Jennifer A.}",
note = "Funding Information: We thank J. Keith (NIH) for the 1B7 and 11E6 hybridomas; D. Ambrosino (Mass Biologics) for P-IVIG; T. Merkel (U.S. Food and Drug Administration) for helpful discussions; H. Sato and Y. Sato for their publications on the m1B7 and m11E6 antibodies. We acknowledge the following funding sources: NIH grant #AI066239, Norman Hackerman Advanced Research Project #003658-0019-2011, Welch F-1767, and Synthetic Biologics (J.A.M.); NIH grant #P40OD010431 and #P40OD010988 (R.F.W.). M.K. and A.B. are employed by Synthetic Biologics, which has a financial interest in hu1B7 and hu11E6 antibodies. J.A.M. has been awarded a patent no. US 20120244144 A1, {"}Pertussis antibodies and uses thereof.{"} J.A.M., A.W.N., E.K.W., and E.A.P. have jointly filed a provisional patent with Synthetic Biologics, {"}Humanized pertussis antibodies and uses thereof,{"} with the U.S. Patent and Trademark Office. This work is supported in part by funding from Synthetic Biologics.",
year = "2015",
month = dec,
day = "2",
doi = "10.1126/scitranslmed.aad0966",
language = "English (US)",
volume = "7",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
number = "316",
}
