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

Ganesh Ingavle; Les W.J. Baillie; Nathan Davies; Nigel Beaton; Yishan Zheng; Sergey Mikhalovsky; Susan Sandeman

doi:10.1038/s41598-018-25678-0

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

Ganesh Ingavle, Les W.J. Baillie, Nathan Davies, Nigel Beaton, Yishan Zheng, Sergey Mikhalovsky, Susan Sandeman

Research output: Contribution to journal › Article › peer-review

Abstract

Whilst various remedial human monoclonal antibodies have been developed to treat the potentiallylife-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 theuse 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 2hours using an in vivo PA rat infusion model. This work provides proof-of-concept evidence to supportthe development of such alternative detoxification platforms.

Original language	English
Article number	7518
Pages (from-to)	1-11
Number of pages	11
Journal	Scientific Reports
Volume	8
DOIs	https://doi.org/10.1038/s41598-018-25678-0
Publication status	Published - 14 May 2018

Bibliographical note

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Susan Sandeman
- S.Sandemanbrighton.acuk
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title = "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 potentiallylife-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 theuse 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 2hours using an in vivo PA rat infusion model. This work provides proof-of-concept evidence to supportthe development of such alternative detoxification platforms.",

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

Abstract

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