Evaluation of antigens for development of a serological test for Human African Trypanosomiasis

TY - JOUR

T1 - Evaluation of antigens for development of a serological test for Human African Trypanosomiasis

AU - Biéler, Sylvain

AU - Waltenberger, Harald

AU - Barrett, Michael P.

AU - McCulloch, Richard

AU - Mottram, Jeremy C.

AU - Carrington, Mark

AU - Schwaeble, Wilhelm

AU - McKerrow, James

AU - Phillips, Margaret A.

AU - Michels, Paul A.

AU - Büscher, Philippe

AU - Sanchez, Jean-Charles

AU - Bishop, Richard

AU - Robinson, Derrick R.

AU - Bangs, James

AU - Ferguson, Michael

AU - Nerima, Barbara

AU - Albertini, Audrey

AU - Michel, Gerd

AU - Radwandska, Magdalena

AU - Ndung'u, Joseph Mathu

N1 - 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-nationalerecherche.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).

PY - 2016/12/9

Y1 - 2016/12/9

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pone.0168074

DO - 10.1371/journal.pone.0168074

M3 - Article

C2 - 27936225

SN - 1932-6203

VL - 11

SP - 1

EP - 23

JO - PLoS ONE

JF - PLoS ONE

IS - 12

M1 - e0168074

ER -