Role of Gamma/Delta T cells in vaccine induced immunity
We identified a microbial ligand mGLP (methylglucolipopolysaccharide) that is produced by virulent TB. This ligand induces a subset of T cells, the gamma delta T cells. The mGLP is now headed for non-human primate studies to evaluate their protective efficacy. Structure to Functional studies is ongoing.
Karen Dobos, Ph.D.
Mycobacteria Research Laboratories, Colorado State University
Daniel Hoft, M.D., Ph.D.
Saint Louis University
TB diagnostic research: Provision and characterization of Lipoarabinomannan from clinical isolates
Our laboratory has been involved in the TB diagnostics for more than a decade. Our group is focused on validation of LAM in clinical samples using capture ELISA (C-ELISA) in paired urine and serum samples using murine and human monoclonal antibodies, essentially relying on LAM as an ‘immuno-marker’; and, secondly, detection of α- D- arabinofuranose and tuberculostearic acid (TBSA)- ‘chemical-markers’ unique to mycobacterial cell wall polysaccharides/lipoglycans by recently developed gas chromatography/mass spectrometry (GC/MS) method. The work is now leading to development of point-of-care tests for developing new generation TB diagnostics.
Emmanuel Moreau, Ph.D.
Foundation for Innovative New Diagnostics (FIND)
Abraham Pinter, Ph.D.
Rutgers New Jersey Medical School
Jacqueline Achkar, M.D., M.Sc., F.I.D.S.A.
Albert Einstein College of Medicine
Molly Franke, Sc.D.
Harvard Medical School
Validation of Urine / Serum LAM in HIV / non-HIV TB suspects and POC test development
Lipoarabinomannan (LAM) is the only WHO-endorsed TB biomarker that can be detected in urine, an easily collected sample. For obtaining optimal sensitivity, we and the others have shown that some form of sample pretreatment is necessary to remove background from patient urine samples. In recent years, we and many other laboratories have clearly shown urinary LAM based diagnostics for active TB to gain significant advances. Specimens like serum and urine collection are less invasive and can be easily collected from patients admitted to the hospital or even outside of the hospital setting. A Point-of- Care (POC) test that readily detects active TB would reduce diagnostic delays, interrupt transmission with appropriate therapy, and address many of the current gaps in global TB control. Our laboratory focuses on validation of a wide range of clinical samples with a simple capture ELISA (C-ELISA) on clinically characterized patient samples to determine the potential correlation between HIV co-infection and test performance, including a proteinase K (ProK) sample pretreatment to alleviate background and open up epitopes if sequestered. This C-ELISA can be implemented in a clinical setting but not as a POC test. Our group is also involved in the pre developmental stages of an LFA based immunoassay and a Capillary driven (microfluidics) enzymatic immunoassay to be developed into a POC test for the TB diagnostics.
Charles Henry, Ph.D
Departments of Chemistry, Chemical & Biological Engineering, Colorado State University
Department of Chemistry, Chulangkorn University, Thailand
Urine Lipoarabinomannan as a marker for low-risk of NTM airway infection
We have an ongoing collaboration with National Jewish (PI Jerry Nick) funded through the Cystic Fibrosis Foundation to test urine LAM as a non-invasive marker for detection of NTM infection in the CF airway. The trial “Painless Trial: Prospective AnalysIs of uriNe LAM to Eliminate NTM Sputum Screening” is an innovative and very timely response to allow for NTM screening in low-risk populations who are less and less able to expectorate sputum. This trial will allow prospective longitudinal assessment to test the correlation of a negative urine LAM with a history of negative NTM sputum cultures and to test the sensitivity of a positive urine LAM to predict a new positive NTM sputum culture. In addition, our group is utilizing the samples and clinical database to develop an ELISA specific for the absence of a NTM positive sputum culture in the CF population. If successful, this method can be further validated in a multi-site trial and rapidly implemented for the CF population nationwide. We have worked closely together for the past two years and would continue our collaboration for the foreseeable future.
Jerry Nick, M.D.
National Jewish Health