Development of lateral flow assays to detect host proteins in cattle for improved diagnosis of bovine tuberculosis

• Published in: Frontiers in veterinary science Vol. 10; p. 1193332
• Main Authors: Khalid, Hamza, Pierneef, Louise, van Hooij, Anouk, Zhou, Zijie, de Jong, Danielle, Tjon Kon Fat, Elisa, Connelley, Timothy K., Hope, Jayne C., Corstjens, Paul L. A. M., Geluk, Annemieke
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 15-08-2023
• Subjects: biomarkers; bovine tuberculosis; chemokines; cytokines; diagnostics; DIVA; Veterinary Science
• ISSN: 2297-1769; 2297-1769
• DOI: 10.3389/fvets.2023.1193332

Bovine tuberculosis (bTB), caused by
Mycobacterium bovis
(
M. bovis
) infection in cattle, is an economically devastating chronic disease for livestock worldwide. Efficient disease control measures rely on early and accurate diagnosis using the tuberculin skin test (TST) and interferon-gamma release assays (IGRAs), followed by culling of positive animals. Compromised performance of TST and IGRA, due to BCG vaccination or co-infections with non-tuberculous mycobacteria (NTM), urges improved diagnostics. Lateral flow assays (LFAs) utilizing luminescent upconverting reporter particles (UCP) for quantitative measurement of host biomarkers present an accurate but less equipment- and labor-demanding diagnostic test platform. UCP-LFAs have proven applications for human infectious diseases. Here, we report the development of UCP-LFAs for the detection of six bovine proteins (IFN-γ, IL-2, IL-6, CCL4, CXCL9, and CXCL10), which have been described by ELISA as potential biomarkers to discriminate
M. bovis
infected from naïve and BCG-vaccinated cattle. We show that, in line with the ELISA data, the combined PPDb-induced levels of IFN-γ, IL-2, IL-6, CCL4, and CXCL9 determined by UCP-LFAs can discriminate
M. bovis
challenged animals from naïve (AUC range: 0.87–1.00) and BCG-vaccinated animals (AUC range: 0.97–1.00) in this cohort. These initial findings can be used to develop a robust and user-friendly multi-biomarker test (MBT) for bTB diagnosis.