title: Pathogen-reduced Ebola virus convalescent plasma: first steps towards standardization of manufacturing and quality control including assessment of Ebola-specific neutralizing antibodies.
abstract: BACKGROUND
  Ebola virus disease is a public health emergency of international concern, and enormous efforts are being made in the development of vaccines and therapies. Ebola virus convalescent plasma is a promising anti-infective treatment of Ebola virus disease. Therefore, we developed and implemented a pathogen-reduced Ebola virus convalescent plasma concept in accordance with national, European and global regulatory framework.
  
  
  METHODS
  Ebola virus convalescent plasma manufacture and distribution was managed by a collection centre, two medical centres and an expert group from the European Blood Alliance. Ebola virus convalescent plasma was collected twice with an interval of 61 days from a donor recovering from Ebola virus disease in Germany. After pathogen reduction, the plasma was analysed for Ebola virus-specific immunoglobulin G (IgG) antibodies and its Ebola virus neutralizing activity.
  
  
  RESULTS
  Convalescent plasma could be collected without adverse events. Anti-Ebola virus IgG titres and Ebola-specific neutralizing antibodies in convalescent plasma were only slightly reduced after pathogen reduction treatment with S59 amotosalen/UVA. A patient in Italy with Ebola virus disease was treated with convalescent plasma without apparent adverse effects.
  
  
  CONCLUSIONS
  As proof of principle, we describe a concept and practical implementation of pathogen-reduced Ebola virus convalescent plasma manufacture, quality control and its clinical application to an Ebola virus disease patient.
authors.affiliation: Institute for Transfusion Medicine and Immunohaematology, German Red Cross Blood Donor Service Baden-Württemberg-Hessen gGmbH, Goethe University Hospital, Frankfurt am Main, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Geisen
authors.affiliation: Department of Infectious Diseases, Goethe University Hospital, Frankfurt am Main, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Kann
authors.affiliation: Institute of Virology, Philipps University Marburg, Marburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Strecker
authors.affiliation: Department of Infectious Diseases, Goethe University Hospital, Frankfurt am Main, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Wolf
authors.affiliation: Department of Infectious Diseases, Goethe University Hospital, Frankfurt am Main, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Schüttfort
authors.affiliation: Sanquin Blood Bank, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Kraaij
authors.affiliation: NHSBT Leeds Centre, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: MacLennan
authors.affiliation: Institute of Transfusion Medicine, University Hospital Jena, Jena, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Rummler
authors.affiliation: Institute of Transfusion Medicine, University Hospital Jena, Jena, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Weinigel
authors.affiliation: Institute of Virology, Philipps University Marburg, Marburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Eickmann
authors.affiliation: Institute of Virology, Philipps University Marburg, Marburg, Germany.
authors.forename: S K
authors.initials: SK
authors.lastname: Fehling
authors.affiliation: Institute of Virology, Philipps University Marburg, Marburg, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Krähling
authors.affiliation: Institute for Transfusion Medicine and Immunohaematology, German Red Cross Blood Donor Service Baden-Württemberg-Hessen gGmbH, Goethe University Hospital, Frankfurt am Main, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Seidl
authors.affiliation: Institute for Transfusion Medicine and Immunohaematology, German Red Cross Blood Donor Service Baden-Württemberg-Hessen gGmbH, Goethe University Hospital, Frankfurt am Main, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Seifried
authors.affiliation: Institute for Transfusion Medicine and Immunohaematology, German Red Cross Blood Donor Service Baden-Württemberg-Hessen gGmbH, Goethe University Hospital, Frankfurt am Main, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Institute for Transfusion Medicine and Immunohaematology, German Red Cross Blood Donor Service Baden-Württemberg-Hessen gGmbH, Goethe University Hospital, Frankfurt am Main, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Schäfer
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000302:isolation & purification* / Q000627:therapeutic use; D001782:Blood Donors; D003289:Convalescence; D029043:Ebolavirus / Q000276:immunology*; D011564:Furocoumarins / Q000494:pharmacology; D005858:Germany; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000302:isolation & purification* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D017319:Photosensitizing Agents / Q000494:pharmacology; D011786:Quality Control; D014466:Ultraviolet Rays; D038301:Virus Inactivation / Q000187:drug effects / Q000528:radiation effects
chemical_list: D057134:Antibodies, Neutralizing; D011564:Furocoumarins; D007074:Immunoglobulin G; D017319:Photosensitizing Agents; C118577:amotosalen
keywords: Ebola virus; apheresis; convalescent plasma; neutralizing antibody; pathogen reduction