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Evaluation of Antigens for Development of a Serological Test for Human African Trypanosomiasis

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posted on 2016-12-14, 11:08 authored by S. Biéler, H. Waltenberger, M. P. Barrett, R. McCulloch, J. C. Mottram, M. Carrington, Wilhelm Schwaeble, J. McKerrow, M. A. Phillips, P. A. Michels, P. Büscher, J-C. Sanchez, R. Bishop, D. R. Robinson, J. Bangs, M. Ferguson, B. Nerima, A. Albertini, G. Michel, M. Radwandska, J. Mathu Ndung’u
Background Control and elimination of human African trypanosomiasis (HAT) can be accelerated through the use of diagnostic tests that are more accurate and easier to deploy. The goal of this work was to evaluate the immuno-reactivity of antigens and identify candidates to be considered for development of a simple serological test for the detection of Trypanosoma brucei gambiense or T. b. rhodesiense infections, ideally both. Methodology/Principal Findings The reactivity of 35 antigens was independently evaluated by slot blot and ELISA against sera from both T. b. gambiense and T. b. rhodesiense infected patients and controls. The antigens that were most reactive by both tests to T. b. gambiense sera were the membrane proteins VSG LiTat 1.3, VSG LiTat 1.5 and ISG64. Reactivity to T. b. rhodesiense sera was highest with VSG LiTat 1.3, VSG LiTat 1.5 and SRA, although much lower than with T. b. gambiense samples. The reactivity of all possible combinations of antigens was also calculated. When the slot blot results of 2 antigens were paired, a VSG LiTat 1.3- ISG75 combination performed best on T. b. gambiense sera, while a VSG LiTat 1.3-VSG LiTat 1.5 combination was the most reactive using ELISA. A combination of SRA and either VSG LiTat 1.3 or VSG LiTat 1.5 had the highest reactivity on T. b. rhodesiense sera according to slot blot, while in ELISA, pairing SRA with either GM6 or VSG LiTat 1.3 yielded the best results. Conclusions This study identified antigens that were highly reactive to T. b. gambiense sera, which could be considered for developing a serological test for gambiense HAT, either individually or in combination. Antigens with potential for inclusion in a test for T. b. rhodesiense HAT were also identified, but because their reactivity was comparatively lower, a search for additional antigens would be required before developing a test for this form of the disease.

Funding

Support was provided by Bill & Melinda Gates Foundation (http://www.gatesfoundation.org/), grant 39524 (JMN); National Institutes of Health (https://www.nih.gov/), grant 2R37AI034432 (MAP); National Institute of Allergy and Infectious Diseases (https://www.niaid.nih.gov/), grants AI035739 and AI056866 (JB); Wellcome Trust (https://wellcome.ac.uk/), grant 101842 (MF); The Sandler Foundation to University of California (JMK); Agence nationale de la recherche (http://www.agence-nationale-recherche.fr/), grant ANR-11-LABX-0024 (DRR); Wellcome Trust Centre for Molecular Parasitology (http://www.gla.ac.uk/researchinstitutes/iii/wtcmp/), grant 104111/Z/14/Z (MPB, RMC and JCM). The funders provided support in the form of salaries for authors JMN, SB, AA, GM, MR, MAP, JB, MF, JMK, DRR, MPB, RMC and JCM, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. HW is an employee of MicroCoat Biotechnologie GmbH. This company was contracted by FIND to evaluate the reactivity of the antigens by slot blot and ELISA against sera. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

History

Citation

PLoS One, 2016 11(12): e0168074.

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Infection, Immunity and Inflammation

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  • VoR (Version of Record)

Published in

PLoS One

Publisher

Public Library of Science

issn

1932-6203

Acceptance date

2016-11-27

Copyright date

2016

Available date

2016-12-14

Publisher version

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0168074

Language

en

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