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

Hamza Khalid, Louise Pierneef, Anouk van Hooij, Zijie Zhou, Danielle de Jong, Elisa M. Tjon Kon Fat, Tim Connelley, Jayne Hope, Paul L. A. M. Corstjens, Annemieke Geluk

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalFrontiers in Veterinary Science
Volume10
Early online date15 Aug 2023
DOIs
Publication statusE-pub ahead of print - 15 Aug 2023

Keywords / Materials (for Non-textual outputs)

  • biomarkers
  • bovine tuberculosis
  • Chemokines
  • Cytokines
  • diagnostics
  • DIVA
  • upconverting reporter particles
  • UCP-LFA

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