Inactivation of Zika virus by solvent/detergent treatment of human plasma and other plasma‐derived products and pasteurization of human serum albumin

Abstract

BACKGROUND In 2016 the World Health Organization declared the mosquito‐borne Zika virus (ZIKV) a “public health emergency of international concern.” ZIKV is a blood‐borne pathogen, which therefore causes concerns regarding the safety of human plasma–derived products due to potential contamination of the blood supply. This study investigated the effectiveness of viral inactivation steps used during the routine manufacturing of various plasma‐derived products to reduce ZIKV infectivity. STUDY DESIGN AND METHODS Human plasma and intermediates from the production of various plasma‐derived products were spiked with ZIKV and subjected to virus inactivation using the identical techniques (either solvent/detergent [S/D] treatment or pasteurization) and conditions used for the actual production of the respective products. Samples were taken and the viral loads measured before and after inactivation. RESULTS After S/D treatment of spiked intermediates of the plasma‐derived products Octaplas(LG), Octagam, and Octanate, the viral loads were below the limit of detection in all cases. The mean log reduction factor (LRF) was at least 6.78 log for Octaplas(LG), at least 7.00 log for Octagam, and at least 6.18 log for Octanate after 60, 240, and 480 minutes of S/D treatment, respectively. For 25% human serum albumin (HSA), the mean LRF for ZIKV was at least 7.48 log after pasteurization at 60°C for 120 minutes. CONCLUSION These results demonstrate that the commonly used virus inactivation processes utilized during the production of human plasma and plasma‐derived products, namely, S/D treatment or pasteurization, are effective for inactivation of ZIKV.

Emerging therapies for hemophilia: controversies and unanswered questions

“…Though current virucidal techniques to date have successfully mitigated the risk of emerging viruses (e.g. West Nile 46 and Zika 47 virus), the risk posed by prions 48 and other unidentified infectious agents remains unknown. Preliminary data also suggest that EHL products may fare better for ITI , both for those who fail with rFVIII and as first-line therapy 22 , 23 .…”

Advances in Developing Therapies to Combat Zika Virus: Current Knowledge and Future Perspectives

“…The convalescent serum should be free from ZIKV and other blood-borne pathogens prior to transfer, therefore heat treatment at 58.0 ± 1.0°C for 590 ± 10 min or solvent/detergent (S/D) treatment is commonly employed. S/D treatment with 1% (wt/wt) tri-n-butyl phosphate (TBP) and 1% (wt/wt) octoxynol-9 at 30.0 ± 1.0°C and pH 6.9–7.4 for 60 min completely inactivated ZIKV ( Kühnel et al, 2017 ). A photochemical, amotosalen, quickly intercalates into DNA and RNA strands and forms covalent adducts with pyrimidine, thereby inhibiting replication and transcription of the virus.…”

Prevention and Control Strategies to Counter Zika Virus, a Special Focus on Intervention Approaches against Vector Mosquitoes—Current Updates

“…Blood transfusion can also disseminate ZIKV if preventive measures have not been taken timely (Vasquez et al, 2016 ). Thus, inactivation of the virus by the way of pasteurization and solvent/detergent treatment along with virus removal using filters with a 40 nm pore size, can effectively reduce viral load in the plasma-derived medicinal products (Blümel et al, 2016 ; Farcet and Kreil, 2017 ; Kühnel et al, 2017 ). Amotosalen combined with UV light has also shown to inactivate ZIKV in fresh or frozen plasma (Aubry et al, 2016 ; Santa Maria et al, 2017 ).…”