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Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons

Pertussis continues to cause considerable infant mortality world-wide, which could be addressed in part by passive immunization strategies. Antibody hu1B7 is a candidate therapeutic that potently neutralizes pertussis toxin in vitro, prevents leukocytosis in mice and treats established disease in we...

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Autores principales: Nguyen, Annalee W., DiVenere, Andrea M., Papin, James F., Connelly, Sheila, Kaleko, Michael, Maynard, Jennifer A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002138/
https://www.ncbi.nlm.nih.gov/pubmed/32076653
http://dx.doi.org/10.1126/sciadv.aay9258
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author Nguyen, Annalee W.
DiVenere, Andrea M.
Papin, James F.
Connelly, Sheila
Kaleko, Michael
Maynard, Jennifer A.
author_facet Nguyen, Annalee W.
DiVenere, Andrea M.
Papin, James F.
Connelly, Sheila
Kaleko, Michael
Maynard, Jennifer A.
author_sort Nguyen, Annalee W.
collection PubMed
description Pertussis continues to cause considerable infant mortality world-wide, which could be addressed in part by passive immunization strategies. Antibody hu1B7 is a candidate therapeutic that potently neutralizes pertussis toxin in vitro, prevents leukocytosis in mice and treats established disease in weanling baboons as part of an antibody cocktail. Here, we evaluated the potential for hu1B7 and an extended half-life hu1B7 variant to prevent death, leukocytosis and other clinical symptoms in a newborn baboon model that mimics many aspects of human disease. We administered a single antibody dose to newborn baboons five weeks prior to experimental infection. While all animals were heavily colonized with Bordetella pertussis, prophylaxed animals showed significantly greater survival (P < 0.005), delayed and suppressed leukocytosis (P < 0.01) and enhanced clinical outcomes, including coughing (P < 0.01), as compared to controls. Together, this work demonstrates that a single neutralizing anti-PTx antibody is sufficient to prevent clinical pertussis symptoms.
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spelling pubmed-70021382020-02-19 Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons Nguyen, Annalee W. DiVenere, Andrea M. Papin, James F. Connelly, Sheila Kaleko, Michael Maynard, Jennifer A. Sci Adv Research Articles Pertussis continues to cause considerable infant mortality world-wide, which could be addressed in part by passive immunization strategies. Antibody hu1B7 is a candidate therapeutic that potently neutralizes pertussis toxin in vitro, prevents leukocytosis in mice and treats established disease in weanling baboons as part of an antibody cocktail. Here, we evaluated the potential for hu1B7 and an extended half-life hu1B7 variant to prevent death, leukocytosis and other clinical symptoms in a newborn baboon model that mimics many aspects of human disease. We administered a single antibody dose to newborn baboons five weeks prior to experimental infection. While all animals were heavily colonized with Bordetella pertussis, prophylaxed animals showed significantly greater survival (P < 0.005), delayed and suppressed leukocytosis (P < 0.01) and enhanced clinical outcomes, including coughing (P < 0.01), as compared to controls. Together, this work demonstrates that a single neutralizing anti-PTx antibody is sufficient to prevent clinical pertussis symptoms. American Association for the Advancement of Science 2020-02-05 /pmc/articles/PMC7002138/ /pubmed/32076653 http://dx.doi.org/10.1126/sciadv.aay9258 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Nguyen, Annalee W.
DiVenere, Andrea M.
Papin, James F.
Connelly, Sheila
Kaleko, Michael
Maynard, Jennifer A.
Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons
title Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons
title_full Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons
title_fullStr Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons
title_full_unstemmed Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons
title_short Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons
title_sort neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002138/
https://www.ncbi.nlm.nih.gov/pubmed/32076653
http://dx.doi.org/10.1126/sciadv.aay9258
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