title: Treatment of blood with a pathogen reduction technology using ultraviolet light and riboflavin inactivates Ebola virus in vitro.
abstract: BACKGROUND
  Transfusion of plasma from recovered patients after Ebolavirus (EBOV) infection, typically called "convalescent plasma," is an effective treatment for active disease available in endemic areas, but carries the risk of introducing other pathogens, including other strains of EBOV. A pathogen reduction technology using ultraviolet light and riboflavin (UV+RB) is effective against multiple enveloped, negative-sense, single-stranded RNA viruses that are similar in structure to EBOV. We hypothesized that UV+RB is effective against EBOV in blood products without activating complement or reducing protective immunoglobulin titers that are important for the treatment of Ebola virus disease (EVD).
  
  
  METHODS
  Four in vitro experiments were conducted to evaluate effects of UV+RB on green fluorescent protein EBOV (EBOV-GFP), wild-type EBOV in serum, and whole blood, respectively, and on immunoglobulins and complement in plasma. Initial titers for Experiments 1 to 3 were 4.21 log GFP units/mL, 4.96 log infectious units/mL, and 4.23 log plaque-forming units/mL. Conditions tested in the first three experiments included the following: 1-EBOV-GFP plus UV+RB; 2-EBOV-GFP plus RB only; 3-EBOV-GFP plus UV only; 4-EBOV-GFP without RB or UV; 5-virus-free control plus UV only; and 6-virus-free control without RB or UV.
  
  
  RESULTS
  UV+RB reduced EBOV titers to nondetectable levels in both nonhuman primate serum (≥2.8- to 3.2-log reduction) and human whole blood (≥3.0-log reduction) without decreasing protective antibody titers in human plasma.
  
  
  CONCLUSIONS
  Our in vitro results demonstrate that the UV+RB treatment efficiently reduces EBOV titers to below limits of detection in both serum and whole blood. In vivo testing to determine whether UV+RB can improve convalescent blood product safety is indicated.
authors.affiliation: Coagulation and Blood Research, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, Texas.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Cap
authors.affiliation: Coagulation and Blood Research, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, Texas.
authors.forename: Heather F
authors.initials: HF
authors.lastname: Pidcoke
authors.affiliation: Terumo BCT, Lakewood, Colorado.
authors.forename: Shawn D
authors.initials: SD
authors.lastname: Keil
authors.affiliation: Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, Texas.
authors.forename: Hilary M
authors.initials: HM
authors.lastname: Staples
authors.affiliation: Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, Texas.
authors.forename: Manu
authors.initials: M
authors.lastname: Anantpadma
authors.affiliation: Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, Texas.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Carrion
authors.affiliation: Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, Texas.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Davey
authors.affiliation: Complement Laboratory, National Jewish Laboratory, Denver, Colorado.
authors.forename: Ashley
authors.initials: A
authors.lastname: Frazer-Abel
authors.affiliation: United States Army Blood Program, JBSA Fort Sam Houston, Texas.
authors.forename: Audra L
authors.initials: AL
authors.lastname: Taylor
authors.affiliation: Terumo BCT, Lakewood, Colorado.|United States Army Blood Program, JBSA Fort Sam Houston, Texas.
authors.forename: Richard
authors.initials: R
authors.lastname: Gonzales
authors.affiliation: Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, Texas.
authors.forename: Jean L
authors.initials: JL
authors.lastname: Patterson
authors.affiliation: Terumo BCT, Lakewood, Colorado.
authors.forename: Raymond P
authors.initials: RP
authors.lastname: Goodrich
mesh_terms: D000818:Animals; D001769:Blood / Q000821:virology*; D002522:Chlorocebus aethiops; D004203:Disinfection / Q000379:methods*; D029043:Ebolavirus; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control*; D006801:Humans; D008252:Macaca fascicularis; D012256:Riboflavin / Q000494:pharmacology*; D014466:Ultraviolet Rays; D014709:Vero Cells; D038301:Virus Inactivation / Q000528:radiation effects*
chemical_list: D012256:Riboflavin