Application of Monoclonal Anti-Mycolate Antibodies in Serological Diagnosis of Tuberculosis

Patient loss to follow-up caused by centralised and expensive diagnostics that are reliant on sputum is a major obstacle in the fight to end tuberculosis. An affordable, non-sputum biomarker-based, point-of-care deployable test is needed to address this. Serum antibodies binding the mycobacterial ce...

Full description

Saved in:
Bibliographic Details
Main Authors: Alma Truyts, Ilse Du Preez, Eldas M. Maesela, Manfred R. Scriba, Les Baillie, Arwyn T. Jones, Kevin J. Land, Jan A. Verschoor, Yolandy Lemmer
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Tropical Medicine and Infectious Disease
Subjects:
Online Access:https://www.mdpi.com/2414-6366/9/11/269
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1846152359184433152
author Alma Truyts
Ilse Du Preez
Eldas M. Maesela
Manfred R. Scriba
Les Baillie
Arwyn T. Jones
Kevin J. Land
Jan A. Verschoor
Yolandy Lemmer
author_facet Alma Truyts
Ilse Du Preez
Eldas M. Maesela
Manfred R. Scriba
Les Baillie
Arwyn T. Jones
Kevin J. Land
Jan A. Verschoor
Yolandy Lemmer
author_sort Alma Truyts
collection DOAJ
description Patient loss to follow-up caused by centralised and expensive diagnostics that are reliant on sputum is a major obstacle in the fight to end tuberculosis. An affordable, non-sputum biomarker-based, point-of-care deployable test is needed to address this. Serum antibodies binding the mycobacterial cell wall lipids, mycolic acids, have shown promise as biomarkers for active tuberculosis. However, anti-lipid antibodies are of low affinity, making them difficult to detect in a lateral flow immunoassay—a technology widely deployed at the point-of-care. Previously, recombinant monoclonal anti-mycolate antibodies were developed and applied to characterise the antigenicity of mycolic acid. We now demonstrate that these anti-mycolate antibodies specifically detect hexane extracts of mycobacteria. Secondary antibody-mediated detection was applied to detect the displacement of the monoclonal mycolate antibodies by the anti-mycolic acid antibodies present in tuberculosis-positive guinea pig and human serum samples. These data establish proof-of-concept for a novel lateral flow immunoassay for tuberculosis provisionally named MALIA—mycolate antibody lateral flow immunoassay.
format Article
id doaj-art-92ea0ca414d0423da8cbb9f8f11a6095
institution Kabale University
issn 2414-6366
language English
publishDate 2024-11-01
publisher MDPI AG
record_format Article
series Tropical Medicine and Infectious Disease
spelling doaj-art-92ea0ca414d0423da8cbb9f8f11a60952024-11-26T18:24:15ZengMDPI AGTropical Medicine and Infectious Disease2414-63662024-11-0191126910.3390/tropicalmed9110269Application of Monoclonal Anti-Mycolate Antibodies in Serological Diagnosis of TuberculosisAlma Truyts0Ilse Du Preez1Eldas M. Maesela2Manfred R. Scriba3Les Baillie4Arwyn T. Jones5Kevin J. Land6Jan A. Verschoor7Yolandy Lemmer8Future Production: Chemicals, Council for Scientific and Industrial Research, Pretoria 0081, South AfricaFuture Production: Chemicals, Council for Scientific and Industrial Research, Pretoria 0081, South AfricaFuture Production: Chemicals, Council for Scientific and Industrial Research, Pretoria 0081, South AfricaFuture Production: Chemicals, Council for Scientific and Industrial Research, Pretoria 0081, South AfricaSchool of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3NB, UKSchool of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3NB, UKGlobal Access Diagnostics, Thurleigh, Bedford MK44 2YA, UKDepartment of Biochemistry, Genetics and Microbiology, University of Pretoria, Pretoria 0002, South AfricaFuture Production: Chemicals, Council for Scientific and Industrial Research, Pretoria 0081, South AfricaPatient loss to follow-up caused by centralised and expensive diagnostics that are reliant on sputum is a major obstacle in the fight to end tuberculosis. An affordable, non-sputum biomarker-based, point-of-care deployable test is needed to address this. Serum antibodies binding the mycobacterial cell wall lipids, mycolic acids, have shown promise as biomarkers for active tuberculosis. However, anti-lipid antibodies are of low affinity, making them difficult to detect in a lateral flow immunoassay—a technology widely deployed at the point-of-care. Previously, recombinant monoclonal anti-mycolate antibodies were developed and applied to characterise the antigenicity of mycolic acid. We now demonstrate that these anti-mycolate antibodies specifically detect hexane extracts of mycobacteria. Secondary antibody-mediated detection was applied to detect the displacement of the monoclonal mycolate antibodies by the anti-mycolic acid antibodies present in tuberculosis-positive guinea pig and human serum samples. These data establish proof-of-concept for a novel lateral flow immunoassay for tuberculosis provisionally named MALIA—mycolate antibody lateral flow immunoassay.https://www.mdpi.com/2414-6366/9/11/269tuberculosisnon-sputum-based diagnosispoint-of-carelateral flow immunoassaybiomarkermycolic acid
spellingShingle Alma Truyts
Ilse Du Preez
Eldas M. Maesela
Manfred R. Scriba
Les Baillie
Arwyn T. Jones
Kevin J. Land
Jan A. Verschoor
Yolandy Lemmer
Application of Monoclonal Anti-Mycolate Antibodies in Serological Diagnosis of Tuberculosis
Tropical Medicine and Infectious Disease
tuberculosis
non-sputum-based diagnosis
point-of-care
lateral flow immunoassay
biomarker
mycolic acid
title Application of Monoclonal Anti-Mycolate Antibodies in Serological Diagnosis of Tuberculosis
title_full Application of Monoclonal Anti-Mycolate Antibodies in Serological Diagnosis of Tuberculosis
title_fullStr Application of Monoclonal Anti-Mycolate Antibodies in Serological Diagnosis of Tuberculosis
title_full_unstemmed Application of Monoclonal Anti-Mycolate Antibodies in Serological Diagnosis of Tuberculosis
title_short Application of Monoclonal Anti-Mycolate Antibodies in Serological Diagnosis of Tuberculosis
title_sort application of monoclonal anti mycolate antibodies in serological diagnosis of tuberculosis
topic tuberculosis
non-sputum-based diagnosis
point-of-care
lateral flow immunoassay
biomarker
mycolic acid
url https://www.mdpi.com/2414-6366/9/11/269
work_keys_str_mv AT almatruyts applicationofmonoclonalantimycolateantibodiesinserologicaldiagnosisoftuberculosis
AT ilsedupreez applicationofmonoclonalantimycolateantibodiesinserologicaldiagnosisoftuberculosis
AT eldasmmaesela applicationofmonoclonalantimycolateantibodiesinserologicaldiagnosisoftuberculosis
AT manfredrscriba applicationofmonoclonalantimycolateantibodiesinserologicaldiagnosisoftuberculosis
AT lesbaillie applicationofmonoclonalantimycolateantibodiesinserologicaldiagnosisoftuberculosis
AT arwyntjones applicationofmonoclonalantimycolateantibodiesinserologicaldiagnosisoftuberculosis
AT kevinjland applicationofmonoclonalantimycolateantibodiesinserologicaldiagnosisoftuberculosis
AT janaverschoor applicationofmonoclonalantimycolateantibodiesinserologicaldiagnosisoftuberculosis
AT yolandylemmer applicationofmonoclonalantimycolateantibodiesinserologicaldiagnosisoftuberculosis