A process for solvent/detergent treatment of plasma for transfusion at blood centers that use a disposable‐bag system

Burnouf, Thierry; Goubran, Hadi; Radosevich, M.; Moussa, Suaad; Gorgy, George; El‐Ekiaby, Magdy

doi:10.1111/j.1537-2995.2006.01035.x

Cited by 35 publications

(40 citation statements)

References 49 publications

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“…These samples underwent virus inactivation using a procedure that retains antibody reactivity [44]. Briefly, 1% Tri( n -butyl)phosphate (TnBP) and 1% Triton X-45 were added to thawed serum samples and incubated at 31°C for 4 h. Sterile castor oil was added, mixed and the samples were centrifuged (3800× g , 30 min).…”

Section: Methodsmentioning

confidence: 99%

Proteomic Selection of Immunodiagnostic Antigens for Human African Trypanosomiasis and Generation of a Prototype Lateral Flow Immunodiagnostic Device

Sullivan

Wall²,

Carrington

et al. 2013

PLoS Negl Trop Dis

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BackgroundThe diagnosis of Human African Trypanosomiasis relies mainly on the Card Agglutination Test for Trypanosomiasis (CATT). While this test is successful, it is acknowledged that there may be room for improvement. Our aim was to develop a prototype lateral flow test based on the detection of antibodies to trypanosome antigens.Methodology/Principal FindingsWe took a non-biased approach to identify potential immunodiagnostic parasite protein antigens. The IgG fractions from the sera from Trypanosoma brucei gambiense infected and control patients were isolated using protein-G affinity chromatography and then immobilized on Sepharose beads. The IgG-beads were incubated with detergent lysates of trypanosomes and those proteins that bound were identified by mass spectrometry-based proteomic methods. This approach provided a list of twenty-four trypanosome proteins that selectively bound to the infection IgG fraction and that might, therefore, be considered as immunodiagnostic antigens. We selected four antigens from this list (ISG64, ISG65, ISG75 and GRESAG4) and performed protein expression trials in E. coli with twelve constructs. Seven soluble recombinant protein products (three for ISG64, two for ISG65 and one each for ISG75 and GRESAG4) were obtained and assessed for their immunodiagnostic potential by ELISA using individual and/or pooled patient sera. The ISG65 and ISG64 construct ELISAs performed well with respect to detecting T. b. gambiense infections, though less well for detecting T. b. rhodesiense infections, and the best performing ISG65 construct was used to develop a prototype lateral flow diagnostic device.Conclusions/SignificanceUsing a panel of eighty randomized T. b. gambiense infection and control sera, the prototype showed reasonable sensitivity (88%) and specificity (93%) using visual readout in detecting T. b. gambiense infections. These results provide encouragement to further develop and optimize the lateral flow device for clinical use.

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Section: Methodsmentioning

confidence: 99%

Proteomic Selection of Immunodiagnostic Antigens for Human African Trypanosomiasis and Generation of a Prototype Lateral Flow Immunodiagnostic Device

Sullivan

Wall²,

Carrington

et al. 2013

PLoS Negl Trop Dis

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“…We have introduced the concept of small-scale (“minipool”) plasma processing methods implementable with minimum infrastructural requirements. We developed viral inactivation and protein purification technologies in single-use equipment to prepare virally safe solvent/detergent-filtered (S/D-F) plasma for transfusion as well as minipool S/D-F cryoprecipitate to treat bleeding disorders [2–4]. Similarly simple technologies are desperately needed to make safe immunoglobulin G (IgG), a product on the Essential Medicine List of the World Health Organization, to treat immune-deficient patients.…”

Section: Introductionmentioning

confidence: 99%

Minipool Caprylic Acid Fractionation of Plasma Using Disposable Equipment: A Practical Method to Enhance Immunoglobulin Supply in Developing Countries

El‐Ekiaby¹,

Vargas

Moussa

et al. 2015

PLoS Negl Trop Dis

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BackgroundImmunoglobulin G (IgG) is an essential plasma-derived medicine that is lacking in developing countries. IgG shortages leave immunodeficient patients without treatment, exposing them to devastating recurrent infections from local pathogens. A simple and practical method for producing IgG from normal or convalescent plasma collected in developing countries is needed to provide better, faster access to IgG for patients in need.Methodology/Principal FindingsIgG was purified from 10 consecutive minipools of 20 plasma donations collected in Egypt using single-use equipment. Plasma donations in their collection bags were subjected to 5%-pH5.5 caprylic acid treatment for 90 min at 31°C, and centrifuged to remove the precipitate. Supernatants were pooled, then dialyzed and concentrated using a commercial disposable hemodialyzer. The final preparation was filtered online by gravity, aseptically dispensed into storage transfusion bags, and frozen at <-20°C. The resulting preparation had a mean protein content of 60.5 g/L, 90.2% immunoglobulins, including 83.2% IgG, 12.4% IgA, and 4.4% IgM, and residual albumin. There was fourfold to sixfold enrichment of anti-hepatitis B and anti-rubella antibodies. Analyses of aggregates (<3%), prekallicrein (5-7 IU/mL), plasmin (26.3 mU/mL), thrombin (2.5 mU/mL), thrombin-like activity (0.011 U/g), thrombin generation capacity (< 223 nM), and Factor XI (<0.01 U/mL) activity, Factor XI/XIa antigen (2.4 ng/g) endotoxin (<0.5 EU/mL), and general safety test in rats showed the in vitro safety profile. Viral validation revealed >5 logs reduction of HIV, BVDV, and PRV infectivity in less than 15 min of caprylic acid treatment.Conclusions/Significance90% pure, virally-inactivated immunoglobulins can be prepared from plasma minipools using simple disposable equipment and bag systems. This easy-to-implement process could be used to produce immunoglobulins from local plasma in developing countries to treat immunodeficient patients. It is also relevant for preparing hyperimmune IgG from convalescent plasma during infectious outbreaks such as the current Ebola virus episode.

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“…Most therapeutic pd HSA preparations are manufactured from human plasma after cryoprecipitation (cryopoor plasma) by ethanol fractionation, sometimes combined with chromatographic steps [38]. These concentrates contain between 95 and 98% HSA, and to get highly pure HSA, additional purification steps are necessary [51].…”

Section: Hsamentioning

confidence: 99%

“…In order to reduce further the risk of viral infection, virus inactivation of whole plasma by use of several chemical agents is performed [9,35]. Solvent (tri-(n-butyl)phosphate)/ detergent (Triton X100) (S/D)-treated plasma [35,37] is the most widely used and the best-documented product for clinical use [38], followed by methylene blue (MB)/UV lighttreated plasma [9]. Riboflavin/light-treated plasma is a newly developed product that have been used in several European countries [39].…”

Section: Whole-blood Plasmamentioning

confidence: 99%

Therapeutic plasma proteins – application of proteomics in process optimization, validation, and analysis of the final product

et al. 2011

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An overview is given on the application of proteomic technology in the monitoring of different steps during the production of therapeutic proteins from human plasma. Recent advances in this technology enable the use of proteomics as an advantageous tool for the validation of already existing processes, the development and fine tuning of new production steps, the characterization and quality control of final products, the detection of both harmful impurities and modifications of the therapeutic protein and the auditing of batch-to-batch variations. Further, use of proteomics for preclinical testing of new products, which can be either recombinant or plasma-derived, is also discussed.

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A process for solvent/detergent treatment of plasma for transfusion at blood centers that use a disposable‐bag system

Abstract: S/D treatment of plasma can be performed in a closed-bag system under conditions that maintain plasma protein quality. The technology is simple, presents advantages over the industrial large-scale S/D plasma process, and could be performed in blood centers.

Cited by 35 publications

References 49 publications

Proteomic Selection of Immunodiagnostic Antigens for Human African Trypanosomiasis and Generation of a Prototype Lateral Flow Immunodiagnostic Device

Proteomic Selection of Immunodiagnostic Antigens for Human African Trypanosomiasis and Generation of a Prototype Lateral Flow Immunodiagnostic Device

Minipool Caprylic Acid Fractionation of Plasma Using Disposable Equipment: A Practical Method to Enhance Immunoglobulin Supply in Developing Countries

Therapeutic plasma proteins – application of proteomics in process optimization, validation, and analysis of the final product

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