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 ebolavirus disease (EVD). STUDY DESIGN AND 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 1–3 were: 4.21 log10 GFP units/mL, 4.96 log10 infectious units per mL, and 4.23 log10 plaque forming units per mL (PFU/mL). Conditions tested in the first three experiments included: 1. EBOV-GFP + UV + RB; 2. EBOV-GFP + RB only; 3 EBOV-GFP + UV only; 4. EBOV-GFP without RB or UV; 5. Virus-free control + UV only; and 6. Virus-free control without RB or UV. RESULTS UV + RB reduced EBOV titers to non-detectable levels in both non-human 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. CONCLUSION 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.

Pathogen Reduction of SARS-CoV-2 Virus in Plasma and Whole Blood using Riboflavin and UV Light

“…Previous studies have demonstrated that R + UV PRT is a potential tool to mitigate the risk of infection from convalescent plasma. An in vitro study conducted with Ebola Virus (EBOV) in serum and whole blood from non-human primates with Ebola disease demonstrated that antibody titers were maintained within protective thresholds after R+UV PRT (15).…”

Our experience in riboflavin and ultraviolet light pathogen reduction technology for platelets: from platelet production to patient care

“…Despite progress in donor screening and laboratory testing, a small risk of bacterial, viral, or protozoal contamination of PLTs persists. There is also a continuous risk from newly emerging blood transfusion–transmitted infectious agents . The application of PRT for blood and blood components has the potential to reduce these risks.…”

“…There is also a continuous risk from newly emerging blood transfusion-transmitted infectious agents. 8,29,30 The application of PRT for blood and blood components has the potential to reduce these risks. There are different PRT methods for plasma, PLTs, RBCs, and WB, either commercially available or under active development.…”

The Role of the Laboratory and Transfusion Service in the Management of Ebola Virus Disease

“…The risk of unusual TTI associated with CP is highlighted by studies of the first EVD CP bank, where most units contained filarial larvae [22]. Furthermore, an added layer of protection can be provided by pathogen reduction techniques, which have been reported to inactivate Ebola virus in vitro [31]. Optimal pathogen reduction techniques are those that minimally affect the therapeutic potential and yet inactivate parasites and infections not routinely tested for.…”