Inactivation of Zika virus in platelet components using amotosalen and ultraviolet A illumination

Transfusion. 2017 Aug;57(8):2016-2025. doi: 10.1111/trf.14161. Epub 2017 Jul 3.

Abstract

Background: 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.

Study design and methods: 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.

Results: The mean ZIKV infectivity titers and RNA loads in platelet components before inactivation were either 4.9 log10 plaque forming units per milliliter, or 4.4 log10 50% tissue culture infective dose per milliliter and 7.5 log10 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.

Conclusion: 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.

MeSH terms

  • Animals
  • Blood Platelets / virology*
  • Chlorocebus aethiops
  • Furocoumarins / pharmacology*
  • Humans
  • Platelet Transfusion / adverse effects
  • RNA, Viral
  • Ultraviolet Rays*
  • Vero Cells
  • Viral Load
  • Virus Inactivation* / drug effects
  • Virus Inactivation* / radiation effects
  • Zika Virus Infection / prevention & control
  • Zika Virus Infection / transmission
  • Zika Virus* / drug effects
  • Zika Virus* / radiation effects

Substances

  • Furocoumarins
  • RNA, Viral
  • amotosalen