Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device

Abstract Whilst various remedial human monoclonal antibodies have been developed to treat the potentially life-threatening systemic complications associated with anthrax infection, an optimal and universally effective administration route has yet to be established. In the later stages of infection w...

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Autores principales:	Ganesh Ingavle, Les Baillie, Nathan Davies, Nigel Beaton, Yishan Zheng, Sergey Mikhalovsky, Susan Sandeman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ac209f59184640c8aeec21b1e78d134b
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spelling	oai:doaj.org-article:ac209f59184640c8aeec21b1e78d134b2021-12-02T15:07:51ZBioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device10.1038/s41598-018-25678-02045-2322https://doaj.org/article/ac209f59184640c8aeec21b1e78d134b2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25678-0https://doaj.org/toc/2045-2322Abstract Whilst various remedial human monoclonal antibodies have been developed to treat the potentially life-threatening systemic complications associated with anthrax infection, an optimal and universally effective administration route has yet to be established. In the later stages of infection when antibody administration by injection is more likely to fail one possible route to improve outcome is via the use of an antibody-bound, adsorbent haemoperfusion device. We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood. In addition, we have demonstrated that continuous extracorporeal blood recirculation through a Valortim-bound haemoperfusion column significantly reduced the blood plasma concentration of anthrax PA over 2 hours using an in vivo PA rat infusion model. This work provides proof-of-concept evidence to support the development of such alternative detoxification platforms.Ganesh IngavleLes BaillieNathan DaviesNigel BeatonYishan ZhengSergey MikhalovskySusan SandemanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ganesh Ingavle Les Baillie Nathan Davies Nigel Beaton Yishan Zheng Sergey Mikhalovsky Susan Sandeman Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device
description	Abstract Whilst various remedial human monoclonal antibodies have been developed to treat the potentially life-threatening systemic complications associated with anthrax infection, an optimal and universally effective administration route has yet to be established. In the later stages of infection when antibody administration by injection is more likely to fail one possible route to improve outcome is via the use of an antibody-bound, adsorbent haemoperfusion device. We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood. In addition, we have demonstrated that continuous extracorporeal blood recirculation through a Valortim-bound haemoperfusion column significantly reduced the blood plasma concentration of anthrax PA over 2 hours using an in vivo PA rat infusion model. This work provides proof-of-concept evidence to support the development of such alternative detoxification platforms.
format	article
author	Ganesh Ingavle Les Baillie Nathan Davies Nigel Beaton Yishan Zheng Sergey Mikhalovsky Susan Sandeman
author_facet	Ganesh Ingavle Les Baillie Nathan Davies Nigel Beaton Yishan Zheng Sergey Mikhalovsky Susan Sandeman
author_sort	Ganesh Ingavle
title	Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device
title_short	Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device
title_full	Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device
title_fullStr	Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device
title_full_unstemmed	Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device
title_sort	bioinspired detoxification of blood: the efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/ac209f59184640c8aeec21b1e78d134b
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Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device

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