Quantitative Rapid Test for Detection and Monitoring of Active Pulmonary Tuberculosis in Nonhuman Primates

Nonhuman primates (NHPs) are relevant models to study the pathogenesis of tuberculosis (TB) and evaluate the potential of TB therapies, but rapid tools allowing diagnosis of active pulmonary TB in NHPs are lacking. This study investigates whether low complexity lateral flow assays utilizing upconver...

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Main Authors: Zijie Zhou, Anouk van Hooij, Richard Vervenne, Claudia C. Sombroek, Elisa M. Tjon Kon Fat, Tom H. M. Ottenhoff, Paul L. A. M. Corstjens, Frank Verreck, Annemieke Geluk
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Biology
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Online Access:https://www.mdpi.com/2079-7737/10/12/1260
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author Zijie Zhou
Anouk van Hooij
Richard Vervenne
Claudia C. Sombroek
Elisa M. Tjon Kon Fat
Tom H. M. Ottenhoff
Paul L. A. M. Corstjens
Frank Verreck
Annemieke Geluk
author_facet Zijie Zhou
Anouk van Hooij
Richard Vervenne
Claudia C. Sombroek
Elisa M. Tjon Kon Fat
Tom H. M. Ottenhoff
Paul L. A. M. Corstjens
Frank Verreck
Annemieke Geluk
author_sort Zijie Zhou
collection DOAJ
description Nonhuman primates (NHPs) are relevant models to study the pathogenesis of tuberculosis (TB) and evaluate the potential of TB therapies, but rapid tools allowing diagnosis of active pulmonary TB in NHPs are lacking. This study investigates whether low complexity lateral flow assays utilizing upconverting reporter particles (UCP-LFAs) developed for rapid detection of human serum proteins can be applied to detect and monitor active pulmonary TB in NHPs. UCP-LFAs were used to assess serum proteins levels and changes in relation to the MTB challenge dosage, lung pathology, treatment, and disease outcome in experimentally MTB-infected macaques. Serum levels of SAA1, IP-10, and IL-6 showed a significant increase after MTB infection in rhesus macaques and correlated with disease severity as determined by pathology scoring. Moreover, these biomarkers could sensitively detect the reduction of bacterial levels in the lungs of macaques due to BCG vaccination or drug treatment. Quantitative measurements by rapid UCP-LFAs specific for SAA1, IP-10, and IL-6 in serum can be utilized to detect active progressive pulmonary TB in macaques. The UCP-LFAs thus offer a low-cost, convenient, and minimally invasive diagnostic tool that can be applied in studies on TB vaccine and drug development involving macaques.
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spelling doaj.art-cfcbe3c23ac7465393b01836dfc193472023-11-23T03:53:19ZengMDPI AGBiology2079-77372021-12-011012126010.3390/biology10121260Quantitative Rapid Test for Detection and Monitoring of Active Pulmonary Tuberculosis in Nonhuman PrimatesZijie Zhou0Anouk van Hooij1Richard Vervenne2Claudia C. Sombroek3Elisa M. Tjon Kon Fat4Tom H. M. Ottenhoff5Paul L. A. M. Corstjens6Frank Verreck7Annemieke Geluk8Department of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsSection of TB Research & Immunology, Biomedical Primate Research Center (BPRC), 2288 GJ Rijswijk, The NetherlandsSection of TB Research & Immunology, Biomedical Primate Research Center (BPRC), 2288 GJ Rijswijk, The NetherlandsDepartment of Cell and Chemical Biology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Cell and Chemical Biology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsSection of TB Research & Immunology, Biomedical Primate Research Center (BPRC), 2288 GJ Rijswijk, The NetherlandsDepartment of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsNonhuman primates (NHPs) are relevant models to study the pathogenesis of tuberculosis (TB) and evaluate the potential of TB therapies, but rapid tools allowing diagnosis of active pulmonary TB in NHPs are lacking. This study investigates whether low complexity lateral flow assays utilizing upconverting reporter particles (UCP-LFAs) developed for rapid detection of human serum proteins can be applied to detect and monitor active pulmonary TB in NHPs. UCP-LFAs were used to assess serum proteins levels and changes in relation to the MTB challenge dosage, lung pathology, treatment, and disease outcome in experimentally MTB-infected macaques. Serum levels of SAA1, IP-10, and IL-6 showed a significant increase after MTB infection in rhesus macaques and correlated with disease severity as determined by pathology scoring. Moreover, these biomarkers could sensitively detect the reduction of bacterial levels in the lungs of macaques due to BCG vaccination or drug treatment. Quantitative measurements by rapid UCP-LFAs specific for SAA1, IP-10, and IL-6 in serum can be utilized to detect active progressive pulmonary TB in macaques. The UCP-LFAs thus offer a low-cost, convenient, and minimally invasive diagnostic tool that can be applied in studies on TB vaccine and drug development involving macaques.https://www.mdpi.com/2079-7737/10/12/1260biomarkersdiagnosisnonhuman primates (NHPs)lateral flow assayup-converting reporter particlesMTB
spellingShingle Zijie Zhou
Anouk van Hooij
Richard Vervenne
Claudia C. Sombroek
Elisa M. Tjon Kon Fat
Tom H. M. Ottenhoff
Paul L. A. M. Corstjens
Frank Verreck
Annemieke Geluk
Quantitative Rapid Test for Detection and Monitoring of Active Pulmonary Tuberculosis in Nonhuman Primates
Biology
biomarkers
diagnosis
nonhuman primates (NHPs)
lateral flow assay
up-converting reporter particles
MTB
title Quantitative Rapid Test for Detection and Monitoring of Active Pulmonary Tuberculosis in Nonhuman Primates
title_full Quantitative Rapid Test for Detection and Monitoring of Active Pulmonary Tuberculosis in Nonhuman Primates
title_fullStr Quantitative Rapid Test for Detection and Monitoring of Active Pulmonary Tuberculosis in Nonhuman Primates
title_full_unstemmed Quantitative Rapid Test for Detection and Monitoring of Active Pulmonary Tuberculosis in Nonhuman Primates
title_short Quantitative Rapid Test for Detection and Monitoring of Active Pulmonary Tuberculosis in Nonhuman Primates
title_sort quantitative rapid test for detection and monitoring of active pulmonary tuberculosis in nonhuman primates
topic biomarkers
diagnosis
nonhuman primates (NHPs)
lateral flow assay
up-converting reporter particles
MTB
url https://www.mdpi.com/2079-7737/10/12/1260
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