Santa Maria Felicia, Laughhunn Andrew, Lanteri Marion C, Aubry Maite, Musso Didier, Stassinopoulos Adonis
Cerus Corporation, Concord, California.
Pôle de Recherche et de Veille sur les Maladies Infectieuses Émergentes, Institut Louis Malardé, Tahiti, Polynésie Française.
Transfusion. 2017 Aug;57(8):2016-2025. doi: 10.1111/trf.14161. Epub 2017 Jul 3.
Concerned over the risk of Zika virus (ZIKV) transfusion transmission, public health agencies recommended the implementation of mitigation strategies for its prevention. Those strategies included the use of pathogen inactivation for the treatment of plasma and platelets. The efficacy of amotosalen/ultraviolet A to inactivate ZIKV in plasma had been previously demonstrated, and the efficacy of inactivation in platelets with the same technology was assumed. These studies quantify ZIKV inactivation in platelet components using amotosalen/ultraviolet A.
Platelet components were spiked with ZIKV, and ZIKV infectious titers and RNA loads were measured by cell culture-based assays and real-time polymerase chain reaction in spiked platelet components before and after photochemical treatment using amotosalen/ultraviolet A.
The mean ZIKV infectivity titers and RNA loads in platelet components before inactivation were either 4.9 log plaque forming units per milliliter, or 4.4 log 50% tissue culture infective dose per milliliter and 7.5 log genome equivalents per milliliter, respectively. No infectivity was detected immediately after amotosalen/ultraviolet A treatment. No replicative virus remained after treatment, as demonstrated by multiple passages on Vero cell cultures; and ZIKV RNA was not detected from the first passage after inactivation. Additional experiments in this study demonstrated efficient inactivation to the limit of detection in platelets manufactured in 65% platelet additive solution, 35% plasma, or 100% plasma.
As previously demonstrated for plasma, robust levels of ZIKV inactivation were achieved in platelet components. With inactivation of higher levels of ZIKV than those reported in asymptomatic, RNA-reactive blood donors, the pathogen-inactivation system using amotosalen/ultraviolet A offers the potential to mitigate the risk of ZIKV transmission by plasma and platelet transfusion.
鉴于寨卡病毒(ZIKV)经输血传播的风险,公共卫生机构建议实施预防缓解策略。这些策略包括使用病原体灭活技术处理血浆和血小板。以往已证明氨甲环酸/紫外线A对血浆中ZIKV的灭活效果,且假定该技术对血小板的灭活效果相同。本研究对使用氨甲环酸/紫外线A的血小板成分中ZIKV的灭活情况进行量化。
向血小板成分中加入ZIKV,在使用氨甲环酸/紫外线A进行光化学处理前后,通过基于细胞培养的检测方法和实时聚合酶链反应,测定加样血小板成分中ZIKV的感染滴度和RNA载量。
灭活前血小板成分中ZIKV的平均感染性滴度分别为每毫升4.9对数蚀斑形成单位,或每毫升4.4对数50%组织培养感染剂量,以及每毫升7.5对数基因组当量。氨甲环酸/紫外线A处理后立即未检测到感染性。如在Vero细胞培养物上多次传代所示,处理后无复制性病毒残留;灭活后第一代未检测到ZIKV RNA。本研究中的其他实验表明,在由65%血小板添加剂溶液、35%血浆或100%血浆制成的血小板中,能有效灭活至检测限。
如先前在血浆中所证明的,血小板成分中实现了高水平的ZIKV灭活。使用氨甲环酸/紫外线A的病原体灭活系统能够灭活比无症状RNA反应性献血者中报告的更高水平的ZIKV,为降低血浆和血小板输血传播ZIKV的风险提供了可能。