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

Ingavle, Ganesh, Baillie, Les, Davies, Nathan, Beaton, Nigel, Zheng, Yishan, Mikhalovsky, Sergey and Sandeman, Susan 2018. Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device. Scientific Reports 8 (1) , 7518. 10.1038/s41598-018-25678-0

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Publisher: Nature Publishing Group
ISSN: 2045-2322
Date of First Compliant Deposit: 29 May 2018
Date of Acceptance: 26 April 2018
Last Modified: 30 May 2018 13:46
URI: http://orca.cf.ac.uk/id/eprint/111803

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