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

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

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Article number966
JournalScience Translational Medicine
Volume7
Issue number316
DOIs
StatePublished - Dec 2 2015

Fingerprint

Whooping Cough
Papio
Pertussis Toxin
Leukocyte Count
Antibodies
Bordetella pertussis
Leukocytosis
Infant Mortality
Developed Countries
Immunosuppression
Immunoglobulins
Vaccination
Monoclonal Antibodies
Anti-Bacterial Agents
Morbidity
Therapeutics

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Nguyen, A. W., Wagner, E. K., Laber, J. R., Goodfield, L. L., Smallridge, W. E., Harvill, E. T., ... Maynard, J. A. (2015). A cocktail of humanized anti-pertussis toxin antibodies limits disease in murine and baboon models of whooping cough. Science Translational Medicine, 7(316), [966]. https://doi.org/10.1126/scitranslmed.aad0966
Nguyen, Annalee W. ; Wagner, Ellen K. ; Laber, Joshua R. ; Goodfield, Laura L. ; Smallridge, William E. ; Harvill, Eric Thomas ; Papin, James F. ; Wolf, Roman F. ; Padlan, Eduardo A. ; Bristol, Andy ; Kaleko, Michael ; Maynard, Jennifer A. / A cocktail of humanized anti-pertussis toxin antibodies limits disease in murine and baboon models of whooping cough. In: Science Translational Medicine. 2015 ; Vol. 7, No. 316.
@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 Thomas} and Papin, {James F.} and Wolf, {Roman F.} and Padlan, {Eduardo A.} and Andy Bristol and Michael Kaleko and Maynard, {Jennifer A.}",
year = "2015",
month = "12",
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",

}

Nguyen, AW, Wagner, EK, Laber, JR, Goodfield, LL, Smallridge, WE, Harvill, ET, Papin, JF, Wolf, RF, Padlan, EA, Bristol, A, Kaleko, M & Maynard, JA 2015, 'A cocktail of humanized anti-pertussis toxin antibodies limits disease in murine and baboon models of whooping cough', Science Translational Medicine, vol. 7, no. 316, 966. https://doi.org/10.1126/scitranslmed.aad0966

A cocktail of humanized anti-pertussis toxin antibodies limits disease in murine and baboon models of whooping cough. / Nguyen, Annalee W.; Wagner, Ellen K.; Laber, Joshua R.; Goodfield, Laura L.; Smallridge, William E.; Harvill, Eric Thomas; Papin, James F.; Wolf, Roman F.; Padlan, Eduardo A.; Bristol, Andy; Kaleko, Michael; Maynard, Jennifer A.

In: Science Translational Medicine, Vol. 7, No. 316, 966, 02.12.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A cocktail of humanized anti-pertussis toxin antibodies limits disease in murine and baboon models of whooping cough

AU - Nguyen, Annalee W.

AU - Wagner, Ellen K.

AU - Laber, Joshua R.

AU - Goodfield, Laura L.

AU - Smallridge, William E.

AU - Harvill, Eric Thomas

AU - Papin, James F.

AU - Wolf, Roman F.

AU - Padlan, Eduardo A.

AU - Bristol, Andy

AU - Kaleko, Michael

AU - Maynard, Jennifer A.

PY - 2015/12/2

Y1 - 2015/12/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84954206789&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84954206789&partnerID=8YFLogxK

U2 - 10.1126/scitranslmed.aad0966

DO - 10.1126/scitranslmed.aad0966

M3 - Article

VL - 7

JO - Science Translational Medicine

JF - Science Translational Medicine

SN - 1946-6234

IS - 316

M1 - 966

ER -