Vox Sanguinis (2016) 111, 456–457 LETTER © 2016 International Society of Blood Transfusion DOI: 10.1111/vox.12445 Convalescent Ebola plasma: assessing neutralizing antibodies at the right stage T. Burnouf, 1 J. M. Dye, 2 J. Ambe, 3 A. Abayomi 3,4 & Global Emerging Pathogens Treatment Consortium (GET) 3 1 Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan 2 US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MA, USA 3 GET, Mainland Hospital, 1 Mainland Hospital Road, Yaba, Lagos, Nigeria 4 Stellenbosch University, Faculty of Medicine and Health Sciences and the National Health Laboratory Services, Tygerberg Hospital, Cape Town Dear Editor, The study of a pathogen-reduction treatment’s impact on Ebola-specific neutralizing antibodies in convalescent plasma collected in Germany is interesting [1]. Plasma was transported to the pathogen inactivation facility and returned to the collection centre for freezing at -40°C within 24 h of collection. Optimal handling of plasma units and samples identified ‘slightly reduced’ Ebola virus (EBOV)-neutralizing antibody activity due to pathogen-reduction treatment. Since statistics were not included in the analysis, assessing whether the reduction, if any, was significant is difficult. Regardless, such ideal processing conditions could not be applied for the data reported in a recent clinical evaluation in Guinea, where convalescent Ebola plasma was collected, pathogen- reduced, and ‘stored at 2~8°C for up to 40 days’ before freezing [2]. The Guinean study identified that convales- cent plasma transfusion did not induce severe adverse reactions but did not significantly improve survival [2]. Unfortunately, the EBOV-neutralizing antibody content was unknown at the time of transfusion and data publi- cation. The challenging conditions faced in Guinea for handling the plasma may have affected Ebola-neutraliz- ing antibodies [3]. We wish to stress that assessing EBOV-neutralizing activity of plasma samples taken immediately before infusion into patients (not right after plasma collection or pathogen reduction) would be essential to clarify impacts of pathogen reduction and long-term liquid storage on Ebola antibody function and clinical outcomes. Although immunoglobulins are regarded as stable pro- teins, there is limited information on the impacts of patho- gen-reduction treatments and storage of clinical plasma on their functional activity. Several pathogen-reduction treatments of clinical plasma use photo-inactivation, a technology not used for viral inactivation of fractionated immunoglobulins. Viral-reduction treatments of fraction- ated immunoglobulins were established to not impact their physiological function according to in vitro and preclinical assays and clinical expertise [4]; in contrast, pathogen- reduction treatments of plasma were developed by mostly evaluating the effects on global coagulation activity and functionality of coagulation factors, meaning that impact on immunoglobulins has not been thoroughly evaluated. Using convalescent plasma subjected to pathogen reduction, as also done in Liberia [5], is fully justified, especially in a challenging epidemiological environment where donors would otherwise be regarded as ineligible for blood donation. Studies to assess the impacts of pathogen-reduction treatments and storage of convales- cent plasma on neutralizing functions of immunoglobu- lins appear justified before drawing conclusions on therapeutic value, or not, of convalescent plasma against EBOV and other emerging infectious agents. The opinions, conclusions, interpretations, and recom- mendations included here are those of the authors and are not necessarily endorsed by the U.S. Army. References 1 Geisen C, Kann G, Strecker T, et al.: Pathogen-reduced Ebola virus convalescent plasma: first steps towards standardization of manufacturing and quality control including assessment of Ebola-specific neutralizing antibodies. Vox Sang 2016; 110: 329–335 2 van Griensven J, Edwards T, de Lamballerie X, et al.: Evalua- tion of convalescent plasma for ebola virus disease in Guinea. N Engl J Med 2016; 374:33–42 3 Burnouf T, Conton B, Dye JM, et al.: Convalescent plasma for ebola virus disease. N Engl J Med 2016; 374:2499 4 Radosevich M, Burnouf T: Intravenous immunoglobulin G: trends in production methods, quality control and quality assurance. Vox Sang 2010; 98:12–28 5 Brown JF, Rowe K, Zacharias P, et al.: Apheresis for collection of ebola convalescent plasma in Liberia. J Clin Apher 2016; doi: 10.1002/jca.21482 Received: 27 July 2016, accepted 30 July 2016 456