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PRIMARY INVESTIGATOR:
Dr. Stefan Kaufmann, Max Planck Institute for Infection Biology, Berlin, Germany - DE
Biomarkers of Protective Immunity Against TB in the Context of HIV/AIDS in Africa
Research ObjectivesProject Progress & Milestones
Collaborators
Project

Tuberculosis (TB) is a major health problem, especially in developing countries. Estimates put the number of people infected with TB at one-third of the world's population, and some 2 million die from the disease each year. In most infected people, TB is latent with only one in 10 infected individuals developing the disease. That percentage increases substantially, however, in those who are infected with both TB and HIV; in Africa, HIV is the single most important factor leading to the increased incidence of TB.

Despite major efforts to effectively treat TB patients and widespread attempts to vaccinate infants against TB, none of the current control strategies address the enormous reservoir of latent infection that continues to perpetuate the disease.
 
Dr. Kaufmann is leading an international consortium that is studying differences in immune system responses between people exposed to TB who never become sick and those who develop the disease, focusing particular attention on people infected with both HIV and TB in endemic African countries. The project's participating laboratories in Europe and the United States are attempting to learn which host responses provide protective immunity against TB and to identify correlates of protective immunity and host biomarkers of TB disease that could help guide the design and testing of improved TB vaccines, drugs, and diagnostics. The team is using sophisticated molecular and immunological tools to study host and pathogen responses to latent TB infection as well as to active disease in individuals living in five African countries.

Project Progress & Milestones:
Researchers have performed genome-wide expression profiling of two different clinical strains of Mycobacterium tuberculosis (MTB) selected from African field sites. They have used in vitro growth conditions that simulate the adaptations that occur in an in vivo microenvironment during three distinct stages of tuberculosis, and have observed significant differences in gene expression profiles during these different stages.
A pilot study of microarray analysis using RNA of CD3+ T cells and peripheral blood mononuclear cells from TB patients, tuberculin skin test positive healthy contacts, and healthy tuberculin skin test negative contacts is near completion. This will allow investigators to select a panel of 40 candidate genes as host biomarkers to be tested in longitudinal field studies.
At four field sites, longitudinal human studies comprising HIV-negative cohorts of newly diagnosed pulmonary TB patients and TB-infected, clinically healthy household contacts are ongoing. An adolescent cohort of 6,321 adolescents from 11 schools in Cape Town, South Africa has been established for an immune correlates study.
HIV-positive cohorts have been established at four field sites and prospective follow-up studies monitoring the kinetics of immune response are ongoing. Researchers have observed lower immune responses in HIV-positive individuals compared to those observed in HIV-negative subjects.
Studies of vaccinated infants and children are underway at three sites. Studies with newborns may help to unravel the mechanisms of protective immune responses induced by the BCG vaccine as well as to identify markers defining the susceptibility to TB disease in vaccinated infants in the endemic population.

Researchers have identified major screening assays and 17 novel potential MTB antigens for use in immune response kinetic studies at seven field sites in Africa.

Investigators have established a Web portal to facilitate both communication between members of the consortium and standardization and harmonization of project protocols and data management.
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Collaborators:
Leiden University, Leiden , Netherlands - NL
Medical Research Council Laboratories, Fajara, Gambia - GM
Stanford University, California, United States - US
Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia - ET
Utrecht University Medical Center, Utrecht, Netherlands - NL
Ethiopian Health and Nutrition Research Institute (EHNRI), Addis Ababa, Ethiopia - ET
Case Western Reserve University, Ohio, United States - US
Makerere University, Kampala, Uganda - UG
London School of Hygiene & Tropical Medicine (LSHTM), London, United Kingdom - GB
Karonga Prevention Study (KPS), Karonga, Malawi - MW
Stellenbosch University, Stellenbosch, South Africa - ZA
University of Cape Town, Cape Town, South Africa - ZA
AERAS, Maryland, United States - US
Statens Serum Institute, Copenhagen, Germany - DE
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 Project at a Glance

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