Inactivation of yellow fever virus in plasma after treatment with methylene blue and visible light and in platelet concentrates following treatment with ultraviolet C light

Abstract

BACKGROUND: Yellow fever virus (YFV) is endemic to tropical and subtropical areas in South America and Africa, and is currently a major public health threat in Brazil. Transfusion transmission of the yellow fever vaccine virus has been demonstrated, which is indicative of the potential for viral transfusion transmission. An approach to manage the potential YFV transfusion transmission risk is the use of pathogen inactivation (PI) technology systems, such as THERAFLEX MB-Plasma and THERAFLEX UV-Platelets (Macopharma). We aimed to investigate the efficacy of these PI technology systems to inactivate YFV in plasma or platelet concentrates (PCs).STUDY DESIGN AND METHODS: YFV spiked plasma units were treated using THERAFLEX MB-Plasma system (visible light doses: 20, 40, 60, and 120 [standard] J/cm 2 ) in the presence of methylene blue (approx. 0.8 μmol/L) and spiked PCs were treated using THERAFLEX UV-Platelets system (ultraviolet C doses: 0.05, 0.10, 0.15, and 0.20 [standard] J/cm 2 ). Samples were taken before the first and after each illumination dose and tested for residual virus using a modified plaque assay. RESULTS: YFV infectivity was reduced by an average of 4.77 log or greater in plasma treated with the THERAFLEX MB-Plasma system and by 4.8 log or greater in PCs treated with THERAFLEX UV-Platelets system. CONCLUSIONS:Our study suggests the THERAFLEX MB-Plasma and the THERAFLEX UV-Platelets systems can efficiently inactivate YFV in plasma or PCs to a similar degree as that for other arboviruses. Given the reduction levels observed in this study, these PI technology systems could be an effective option for managing YFV transfusion-transmission risk in plasma and PCs.ABBREVIATIONS: FBS = fetal bovine serum; PCs = platelet concentrates; PI = pathogen inactivation; YFV = yellow fever virus.From the

Inactivation of yellow fever virus with amotosalen and ultraviolet A light pathogen‐reduction technology

“…In addition, while platelets are resuspended in PAS in Europe and in PAS or in 100% plasma in North America, in Latin America, which is most impacted by YFV outbreaks, platelet manufacturing is in 100% plasma, and this is the first demonstration of PR technology to inactivate YFV in PC‐Plasma. A previous study by Faddy et al reported YFV‐17D inactivation levels of greater than 4.77 log in plasma treated with the THERAFLEX MB‐Plasma system and greater than 4.8 log in PC resuspended in 30% plasma/70% PAS treated with THERAFLEX UV‐Platelets. We report here higher levels of inactivation using the INTERCEPT Blood System for platelets, which is currently used routinely in more than 30 countries and has been reported to be efficacious at inactivating other arboviruses that often cocirculate in impacted areas.…”

Inactivation of Japanese encephalitis virus in plasma by methylene blue combined with visible light and in platelet concentrates by ultraviolet C light

“…These results are similar to studies with other arboviruses, in which infectivity of DENV was reduced by at least 4.46 log, CHIKV by at least 6.58 log , ZIKV by at least 5.68 log, and YFV by at least 4.77 log. 11,13,14 F I G U R E 1 JEV plaque formation before and after treatment with the THERAFLEX systems detected by immunoplaque assay on Vero cells. Representative plaques formed by JEV at 1:10 viral dilution in plasma treated with the THERAFLEX MB-Plasma system using different illumination doses (left) and in PCs treated with the THERAFLEX UV-Platelet system using different illumination doses We also show that on average, the THERAFLEX UV-Platelets system can reduce JEV infectivity in PCs by 7.02 log.…”

“…Only plasma and PCs that tested negative for JEV IgG and IgM were used, and these were treated as described previously. [11][12][13][14] PC quality control variables including platelet count, unit volume, swirl, and pH were assessed. 12,18 1.2 | Cell culture African green monkey kidney cells (Vero; ATCC# CCL-81) were grown in culture and treated as described previously.…”

“…12,18 1.2 | Cell culture African green monkey kidney cells (Vero; ATCC# CCL-81) were grown in culture and treated as described previously. [11][12][13][14] 1.3 | Viral production Japanese encephalitis virus Fu strain (Genbank Accession Number AF217620.1) 19 was grown to 7 × 10 7 PFU/mL by propagation in Vero cells. Virus culture supernatants were harvested 5 days postinfection and clarified by centrifugation.…”

“…Macopharma has developed a PI method for plasma called the THERAFLEX MB-Plasma system and a system for platelets called the THERAFLEX UV-Platelets system, which have been shown to inactivate other arboviruses, including ZIKV, DENV, and chikungunya virus. [11][12][13][14] The former uses a combination of methylene blue (MB) and visible light; the MB intercalates into the guanosine-cytosine pairs in the viral RNA and the visible light causes generation of singlet oxygen that leads to guanosine oxidation causing breakage of the viral RNA. 15,16 The latter uses UVC, which induces the formation of cyclobutane pyrimidine dimers, such as uracil dimers in RNA, disrupting viral RNA transcription and thereby the virus becomes defective.…”