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bioRxiv · 10.1101/2024.12.14.628469

Rapid Sterilization of Clinical Apheresis Blood Products using Ultra-High Dose Rate Radiation

Melemenidis, S.·Nguyen, K. D.·Baraceros-Pineda, R.·Barclay, C. K.·Bautista, J.·Lau, H.·Ashraf, R. M.·Manjappa, R.·Dutt, S.·Soto, L. A.·Katila, N.·Lau, B.·Visvanathan, V.·Yu, A. S.·Surucu, M.·Skinner, L. B.·Engleman, E. G.·Loo, B. W.·Pham, T. D.
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Abstract

BACKGROUND AND OBJECTIVESApheresis platelets products and plasma are essential for medical interventions, but both still have inherent risks associated with contamination and viral transmission. Platelet products are vulnerable to bacterial contamination due to storage conditions, while plasma requires extensive screening to minimize virus transmission risks. Here we investigate rapid irradiation to sterilizing doses for bacteria and viruses as an innovative pathogen reduction technology. MATERIALS AND METHODSWe configured a clinical linear accelerator to deliver ultra-high dose rate (6 kGy/min) irradiation to platelet and plasma blood components. Platelet aliquots spiked with 105 CFU of E.coli were irradiated with 0.1-20 kGy, followed by E.coli growth and platelet count assays. COVID Convalescent Plasma (CCP) aliquots were irradiated at a virus-sterilizing dose of 25 kGy and subsequently, RBD- specific antibody binding was assessed. RESULTS1 kGy irradiation of bacteria-spiked platelets reduced E.coli growth by 2.7- log without significant change of platelet count, and 5 kGy or higher produced complete growth suppression. The estimated sterilization (6-log bacterial reduction) dose was 2.3 kGy, corresponding to 31% platelet count reduction. A 25 kGy virus sterilizing dose to CCP produced a 9.2% average drop of RBD-specific IgG binding. CONCLUSIONThis study shows proof-of-concept of a novel rapid blood sterilization technique using a clinical linear accelerator. Promising platelet counts and CCP antibody binding were maintained at bacteria and virus sterilizing doses, respectively. This represents a potential point-of-care blood product sterilization solution. If additional studies corroborate these findings, this may be a practical method for ensuring blood products safety. HIGHLIGHTSO_LI1 kGy irradiation of bacteria-spiked platelets reduced E.coli growth by 2.7-log without significant change of platelet count, and 5 kGy or higher produced complete growth suppression. C_LIO_LIThe estimated sterilization (6-log bacterial reduction) dose was 2.3 kGy, corresponding to 31% platelet count reduction. C_LIO_LIA 25 kGy virus sterilizing dose to CCP produced a 9.2% average drop of RBD- specific IgG binding. C_LI

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Melemenidis, S., Nguyen, K. D., Baraceros-Pineda, R., Barclay, C. K., Bautista, J., Lau, H., Ashraf, R. M., Manjappa, R., Dutt, S., Soto, L. A., Katila, N., Lau, B., Visvanathan, V., Yu, A. S., Surucu, M., Skinner, L. B., Engleman, E. G., Loo, B. W., Pham, T. D.. 2024-12-14. Rapid Sterilization of Clinical Apheresis Blood Products using Ultra-High Dose Rate Radiation. https://doi.org/10.1101/2024.12.14.628469

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