Grand Challenge #6-74 Biomarkers of Protective Immunity Against TB in the Context of HIV/AIDS in Africa
Information:
Sponsor - The Bill and Melinda Gates Foundation
Principal Investigator - Stefan H.E. Kaufmann, Ph.D., Max Planck Institute for Infection Biology; Co-Investigator - W. Henry Boom, M.D., CWRU
| Type of Study | Observational |
|---|---|
| Design | Longitudinal nested case-control cohort study with 2 year follow-up |
| Project Site | Uganda, The Gambia, Malawi, South Africa, Ethiopia |
| Sample Size | Total across sites: 1098 HIV- patients with active TB, 4690 household contacts and controls with and without LTBI, 359 HIV+ TB patients and 895 HIV+ household contacts and controls without TB |
| Population | Adults with a culture confirmed , initial case of clinically active tuberculosis and adult members of their households without TB disease |
| Study Period | 2006-2012 |
| Interactions | The TBRU enrolled subjects for the GC-6 studies through the Uganda-CWRU Research Collaboration. Additionally, the TBRU data coordinating center has managed the combined data from all participating field sites in Africa to produce a comprehensive database that can be used by GC6 researchers to develop and test hypotheses regarding the host response to TB infection and disease. |
Goal of Study:
The aim of this study is to learn which immunological responses provide protective immunity to TB in order to facilitate the discovery of new TB vaccines.
Objectives of Study:
- To compare biomarker responses between household contact participants that have natural immunity against active TB disease and household contact participants who progress to active disease within the 2 year follow-up time. Markers that differ between groups are potentially useful as correlates of protection
- To compare biomarker responses in HIV positive participants without active disease who control the infection compared to those HIV positive participants who progress to active disease over the 2 year follow-up and assess the effects of ART and treatment of latent infection on biomarker responses
Published Papers:
Musvosvi M, Huang H, Wang C, GC6-74 Consortium, Adolescent Cohort Study team. T cell receptor repertoires associated with control and disease progression following Mycobacterium tuberculosis infection. Nat Med 29, 258–269 (2023). https://doi.org/10.1038/
Meier S, Seddon JA, Maasdorp E, Kleynhans L, du Plessis N, Loxton AG, Malherbe, ST, Zak, DE, Thompson E, Duffy FJ, Kaufmann SHE, Ottenhoff THM, Scriba TJ, Suliman S, Sutherland JS, Winter J, Kuivaniemi H, Walzl G, Tromp, G, GC6-74 Consortium, Catalysis TB Biomarkers Consortium. Neutrophil degranulation, NETosis and platelet degranulation pathway genes are co-induced in whole blood up to six months before tuberculosis diagnosis. PLoS ONE. 2022 17(12): e0278295. https://doi.org/10.1371/
Sutherland JS, Lalor MK, Black GF, Ambrose LR, Loxton AG, Chegou NN, Kassa D, Mihret A, Howe R, Mayanja-Kizza H, Gomez MP, Donkor S, Franken K, Hanekom W, Klein MR, Parida S, Boom WH, Thiel BA, Crampin AC, Ota M, Walzl G, Ottenhoff THM, Dockrell HM, Kaufmann SHE and the GCGH Biomarkers for TB consortium. Analysis of Host Responses to Mycobacterium tuberculosis Antigens in a Multi-Site Study of Subjects with Different TB and HIV Infection States in Sub-Saharan Africa. PLoS ONE 2013, 8(9): e74080. https://doi.org/10.1371/
Black, GF, Thiel, BA, Ota, MO, Parida, SK, Adegbola, R, Boom, WH, Dockrell, HM, Kees, LMC, Friggen, AH, Hill, PC, Klein, MR, Lalor, MK, Mayanja, H, Schoolnik, G, Stanley, K, Weldingh, K, Kaufmann, SHE, Walzl, G, Ottenhoff, THM, and the GCGH Biomarkers for TB Consortium. Immunogenicity of Novel DosR Regulon-Encoded Candidate Antigens of Mycobacterium tuberculosis in Three High-Burden Populations in Africa. 2009. Clinical and Vaccine Immunology 16:1203-1212. PMID: 19553548