Christina L Dean1, Jay W Hooper2, John M Dye2, Samantha E Zak2, Scott A Koepsell3, Laurence Corash4, Richard J Benjamin4, Steve Kwilas2, Shannon Bonds1, Anne M Winkler5, Colleen S Kraft1. 1. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. 2. Division of Virology, US Army Medical Research Institute for Infectious Diseases, Fort Detrick, Maryland, USA. 3. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA. 4. Cerus Corporation, Concord, California, USA. 5. Instrumentation Laboratory, Bedford, Massachusetts, USA.
Abstract
BACKGROUND: In 2014, passive immunization by transfusion of Ebola convalescent plasma (ECP) was considered for treating patients with acute Ebola virus disease (EVD). Early Ebola virus (EBOV) seroconversion confers a survival advantage in natural infection, hence transfusion of ECP plasma with high levels of neutralizing EBOV antibodies is a potential passive immune therapy. Techniques to reduce the risk of other transfusion-transmitted infections (TTIs) are warranted as recent ECP survivors are ineligible as routine blood donors. As part of an ongoing clinical trial to evaluate the safety and effectiveness of ECP, the impact of amotosalen/UVA pathogen reduction technology (PRT) on EBOV antibody characteristics was examined. STUDY DESIGN AND METHODS: Serum and plasma samples were collected from EVD-recovered subjects at multiple timepoints and evaluated by ELISA for antibodies to recombinant EBOV glycoprotein (GP) and irradiated whole EBOV antigen, as well as for EBOV microneutralization, classic plaque reduction neutralization test (PRNT) and EBOV pseudovirion neutralization assay (PsVNA) activity. RESULTS: Six subjects donated 40 individual ECP units. Substantial antibody titers and neutralizing activity results were demonstrated but were generally lower for the ACD plasma samples compared to the serum samples. Anti-EBOV titers by all assays remained essentially unchanged after PRT. CONCLUSION: Treatment of ECP with PRT to reduce the risk of TTI did not significantly reduce EBOV IgG antibody titers or neutralizing activity. Although ECP was used in the treatment of repatriated patients, no PRT units from this study were transfused to EVD patients. This inventory of PRT-treated ECP is currently available for future clinical evaluation.
BACKGROUND: In 2014, passive immunization by transfusion of Ebola convalescent plasma (ECP) was considered for treating patients with acute Ebola virus disease (EVD). Early Ebola virus (EBOV) seroconversion confers a survival advantage in natural infection, hence transfusion of ECP plasma with high levels of neutralizing EBOV antibodies is a potential passive immune therapy. Techniques to reduce the risk of other transfusion-transmitted infections (TTIs) are warranted as recent ECP survivors are ineligible as routine blood donors. As part of an ongoing clinical trial to evaluate the safety and effectiveness of ECP, the impact of amotosalen/UVA pathogen reduction technology (PRT) on EBOV antibody characteristics was examined. STUDY DESIGN AND METHODS: Serum and plasma samples were collected from EVD-recovered subjects at multiple timepoints and evaluated by ELISA for antibodies to recombinant EBOV glycoprotein (GP) and irradiated whole EBOV antigen, as well as for EBOV microneutralization, classic plaque reduction neutralization test (PRNT) and EBOV pseudovirion neutralization assay (PsVNA) activity. RESULTS: Six subjects donated 40 individual ECP units. Substantial antibody titers and neutralizing activity results were demonstrated but were generally lower for the ACD plasma samples compared to the serum samples. Anti-EBOV titers by all assays remained essentially unchanged after PRT. CONCLUSION: Treatment of ECP with PRT to reduce the risk of TTI did not significantly reduce EBOV IgG antibody titers or neutralizing activity. Although ECP was used in the treatment of repatriated patients, no PRT units from this study were transfused to EVD patients. This inventory of PRT-treated ECP is currently available for future clinical evaluation.
Authors: Eric Salazar; Suresh V Kuchipudi; Paul A Christensen; Todd Eagar; Xin Yi; Picheng Zhao; Zhicheng Jin; S Wesley Long; Randall J Olsen; Jian Chen; Brian Castillo; Christopher Leveque; Dalton Towers; Jason Lavinder; Jimmy Gollihar; Jose Cardona; Gregory Ippolito; Ruth Nissly; Ian Bird; Denver Greenawalt; Randall M Rossi; Abhinay Gontu; Sreenidhi Srinivasan; Indira Poojary; Isabella M Cattadori; Peter J Hudson; Nicole M Josleyn; Laura Prugar; Kathleen Huie; Andrew Herbert; David W Bernard; John M Dye; Vivek Kapur; James M Musser Journal: J Clin Invest Date: 2020-12-01 Impact factor: 14.808
Authors: Alexander I Kostin; Maria N Lundgren; Andrey Y Bulanov; Elena A Ladygina; Karina S Chirkova; Alexander L Gintsburg; Denis Y Logunov; Inna V Dolzhikova; Dmitry V Shcheblyakov; Natalia V Borovkova; Mikhail A Godkov; Alexey I Bazhenov; Valeriy V Shustov; Alina S Bogdanova; Alina R Kamalova; Vladimir V Ganchin; Eugene A Dombrovskiy; Stanislav E Volkov; Nataliya E Drozdova; Sergey S Petrikov Journal: Vox Sang Date: 2021-03-18 Impact factor: 2.996
Authors: Kenneth Danh; Donna Grace Karp; Peter V Robinson; David Seftel; Mars Stone; Graham Simmons; Anil Bagri; Martin Schreibman; Andreas Buser; Andreas Holbro; Manuel Battegay; Laurence M Corash; Carl Hanson; Cheng-Ting Tsai Journal: medRxiv Date: 2020-06-02
Authors: Eric Salazar; Suresh V Kuchipudi; Paul A Christensen; Todd N Eagar; Xin Yi; Picheng Zhao; Zhicheng Jin; S Wesley Long; Randall J Olsen; Jian Chen; Brian Castillo; Christopher Leveque; Dalton M Towers; Jason Lavinder; Jimmy D Gollihar; Jose Cardona; Gregory C Ippolito; Ruth H Nissly; Ian M Bird; Denver Greenawalt; Randall M Rossi; Abinhay Gontu; Sreenidhi Srinivasan; Indira B Poojary; Isabella M Cattadori; Peter J Hudson; Nicole Joselyn; Laura Prugar; Kathleen Huie; Andrew Herbert; David W Bernard; John Dye; Vivek Kapur; James M Musser Journal: bioRxiv Date: 2020-06-09
Authors: Shawn D Keil; Izabela Ragan; Susan Yonemura; Lindsay Hartson; Nicole K Dart; Richard Bowen Journal: Vox Sang Date: 2020-05-14 Impact factor: 2.996