@article{280948421baf4598a3cdb24f7d337f2c,
title = "A Serological Point-of-Care Test for the Detection of IgG Antibodies against Ebola Virus in Human Survivors",
abstract = "Ebola virus disease causes widespread and highly fatal epidemics in human populations. Today, there is still great need for point-of-care tests for diagnosis, patient management and surveillance, both during and post outbreaks. We present a point-of-care test comprising an immunochromatographic strip and a smartphone reader, which detects and semiquantifies Ebola-specific antibodies in human survivors. We developed a Sudan virus glycoprotein monoplex platform and validated it using sera from 90 human survivors and 31 local noninfected controls. The performance of the glycoprotein monoplex was 100% sensitivity and 98% specificity compared to standard whole antigen enzyme-linked immunosorbent assay (ELISA), and it was validated with freshly collected patient samples in Uganda. Moreover, we constructed a multiplex test for simultaneous detection of antibodies against three recombinant Sudan virus proteins. A pilot study comprising 15 survivors and 5 noninfected controls demonstrated sensitivity and specificity of 100% compared to standard ELISA. Finally, we developed a second multiplex subtype assay for the identification of exposure to three related EVD species: Sudan virus, Bundibugyo virus and Ebola virus (formerly Zaire) using recombinant viral glycoprotein. This multiplex test could distinguish between the host's immunity to specific viral species and identify cross-reactive immunity. These developed serological platforms consisted of capture ligands with high specificity and sensitivity, in-house developed strips and a compatible smartphone application. These platforms enabled rapid and portable testing, data storage and sharing as well as geographical tagging of the tested individuals in Uganda. This platform holds great potential as a field tool for diagnosis, vaccine development, and therapeutic evaluation.",
keywords = "Ebola virus disease, IgG antibodies, diagnostic test, lateral flow, multiplex, serological point-of-care, smartphone reader",
author = "Polina Brangel and Ariel Sobarzo and Claudio Parolo and Miller, {Benjamin S.} and Howes, {Philip D.} and Sigal Gelkop and Lutwama, {Julius J.} and Dye, {John M.} and McKendry, {Rachel A.} and Leslie Lobel and Stevens, {Molly M.}",
note = "Funding Information: This work was kindly supported by the i-sense EPSRC IRC in Early Warning Sensing Systems for Infectious Disease grant (EP/K031953/1) to M.M.S. and R.A.M. A.S., J.J.L., J.M.D., and L.L. would like to acknowledge the kind support of the United States Defense Threat Reduction Agency (CB10138). Opinions, conclusions, interpretations, and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army. The mention of trade names or commercial products does not constitute endorsement or recommendation for use by the Department of the Army or the Department of Defense. We also wish to thank I. Hartmann for his assistance with the graphic design of the smartphone app. P.B. acknowledges support from the Imperial College Department of Materials Kryszek/Staislawa Scholarship. We would also like to thank M. Dubois, M. Thomas, O. Varasaneux, C. Keane, A. Nogiwa Valdez, B. Pierce and S. Skeete for helpful input. Raw data are available upon request from rdm-enquiries@imperial.ac.uk. Funding Information: P.B. and A.S. designed the study. P.B. conducted all the experimental work, carried out data interpretation and manuscript preparation and writing. A.S., J.J.L., and J.M.D. performed sample collection and preparation, and aided in data interpretation and discussions. The ELISA results of the known samples were a subset of the samples tested and analyzed by A.S. and L.L. in their previously published studies.12,25 C.P. assisted with the development and production of the lateral flow strips in R.A.M{\textquoteright}s lab and helped with discussions. B.M. developed the smartphone app with help from R.A.M. M.M.S. acknowledges the ERC Seventh Framework Programme Consolidator grant “Naturale CG” under grant agreement no. 616417. P.H. aided with discussions, data interpretation, and manuscript writing. S.G. and J.M.D provided the recombinant viral proteins and the monoclonal antibodies. R.A.M., L.L., and M.M.S. supervised the study, aided with study design, data interpretation and revised the manuscript. All authors discussed the results and commented on the manuscript. Notes The authors declare no competing financial interest. Funding Information: 1. Ethics Statement. This study was approved by the Helsinki committees of the Uganda Virus Research Institute in Entebbe, Uganda (reference number GC/127/13/01/15); Soroka Hospital, Beer-sheva, Israel (protocol number 0263−13-SOR); and the Ugandan National Council for Science and Technology (UNCST) (registration number HS1332). L.L. and J.J.L are responsible for all ethical approvals. Written informed consent, as well as a personal health questionnaire, was completed for each subject under the supervision of L.L. and J.J.L. Publisher Copyright: {\textcopyright} 2018 American Chemical Society.",
year = "2018",
month = jan,
day = "23",
doi = "10.1021/acsnano.7b07021",
language = "English",
volume = "12",
pages = "63--73",
journal = "ACS Nano",
issn = "1936-0851",
publisher = "American Chemical Society",
number = "1",
}
