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

Sylvain Biéler; Harald Waltenberger; Michael P. Barrett; Richard McCulloch; Jeremy C. Mottram; Mark Carrington; Wilhelm Schwaeble; James McKerrow; Margaret A. Phillips; Paul A. Michels; Philippe Büscher; Jean-Charles Sanchez; Richard Bishop; Derrick R. Robinson; James Bangs; Michael Ferguson; Barbara Nerima; Audrey Albertini; Gerd Michel; Magdalena Radwandska; Joseph Mathu Ndung'u

doi:10.1371/journal.pone.0168074

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

Sylvain Biéler (Lead / Corresponding author), Harald Waltenberger, Michael P. Barrett, Richard McCulloch, Jeremy C. Mottram, Mark Carrington, Wilhelm Schwaeble, James McKerrow, Margaret A. Phillips, Paul A. Michels, Philippe Büscher, Jean-Charles Sanchez, Richard Bishop, Derrick R. Robinson, James Bangs, Michael Ferguson, Barbara Nerima, Audrey Albertini, Gerd Michel, Magdalena RadwandskaJoseph Mathu Ndung'u

Biological Chemistry and Drug Discovery

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

343 Downloads (Pure)

Abstract

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.

Original language	English
Article number	e0168074
Pages (from-to)	1-23
Number of pages	23
Journal	PLoS ONE
Volume	11
Issue number	12
DOIs	https://doi.org/10.1371/journal.pone.0168074
Publication status	Published - 9 Dec 2016

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1371/journal.pone.0168074Licence: CC BY

Final Published Version
© 2016 Biéler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Final published version, 4.46 MBLicence: CC BY

Protein Glycosylation in Trypanosomes: Defining and Exploiting a Biological System (Senior Investigator Award)
Ferguson, M. (Investigator)
1/10/13 → 30/06/23
Project: Research

Cite this

Biéler, S., Waltenberger, H., Barrett, M. P., McCulloch, R., Mottram, J. C., Carrington, M., Schwaeble, W., McKerrow, J., Phillips, M. A., Michels, P. A., Büscher, P., Sanchez, J.-C., Bishop, R., Robinson, D. R., Bangs, J., Ferguson, M., Nerima, B., Albertini, A., Michel, G., ... Ndung'u, J. M. (2016). Evaluation of antigens for development of a serological test for Human African Trypanosomiasis. PLoS ONE, 11(12), 1-23. Article e0168074. https://doi.org/10.1371/journal.pone.0168074

@article{6ab68f9edaa54bb7bb9116a8fb9ba563,

title = "Evaluation of antigens for development of a serological test for Human African Trypanosomiasis",

abstract = "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.",

author = "Sylvain Bi{\'e}ler and Harald Waltenberger and Barrett, {Michael P.} and Richard McCulloch and Mottram, {Jeremy C.} and Mark Carrington and Wilhelm Schwaeble and James McKerrow and Phillips, {Margaret A.} and Michels, {Paul A.} and Philippe B{\"u}scher and Jean-Charles Sanchez and Richard Bishop and Robinson, {Derrick R.} and James Bangs and Michael Ferguson and Barbara Nerima and Audrey Albertini and Gerd Michel and Magdalena Radwandska and Ndung'u, {Joseph Mathu}",

note = "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).",

year = "2016",

month = dec,

day = "9",

doi = "10.1371/journal.pone.0168074",

language = "English",

volume = "11",

pages = "1--23",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "12",

}

Biéler, S, Waltenberger, H, Barrett, MP, McCulloch, R, Mottram, JC, Carrington, M, Schwaeble, W, McKerrow, J, Phillips, MA, Michels, PA, Büscher, P, Sanchez, J-C, Bishop, R, Robinson, DR, Bangs, J, Ferguson, M, Nerima, B, Albertini, A, Michel, G, Radwandska, M & Ndung'u, JM 2016, 'Evaluation of antigens for development of a serological test for Human African Trypanosomiasis', PLoS ONE, vol. 11, no. 12, e0168074, pp. 1-23. https://doi.org/10.1371/journal.pone.0168074

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 -

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

Abstract

UN SDGs

Access to Document

Fingerprint

Projects

Protein Glycosylation in Trypanosomes: Defining and Exploiting a Biological System (Senior Investigator Award)

Cite this