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Celebrating 100 Years of Health Sciences
Tackling Critical Questions
in TB Vaccine Research in
SATVI
To implement themission of the South African Tuberculosis
Vaccine Initiative (SATVI) – "Innovative and high-quality
TB vaccine research in Africa, to impact the global
epidemic" – a research group, led by Professor
Willem
Hanekom
and Dr
Tom Scriba
, has been testing six new
TB vaccine candidates in 15 completed or ongoing
clinical trials. SATVI also addresses other critical clinical,
epidemiological, immunological and human genetic
questions in TB vaccine development.
Research at the
Intersection of TB and HIV
HIV has driven a dramatic resurgence of the TB
epidemic and a quarter of all HIV-associated TB cases
globally are diagnosed in South Africa.
Research Projects
A large focus of the latter research is identification of
markers in blood to indicate whether a person is at
risk of developing TB disease, or protected against
TB disease: so-called correlates of risk of disease or
of protection. SATVI has emerged as a world-leading
research group in this area, evidenced by multiple
grants awarded from the National Institutes of Health,
the European and Developing Countries Clinical Trials
Partnership (EDCTP), and the Bill and Melinda Gates
Foundation. For example, in 2012, the Director of
SATVI, Professor Willem Hanekom, was awarded a
$4.77 million grant from the Gates Foundation, while
SATVI’s Deputy Director for Immunology and Human
Genetics, Dr Tom Scriba, was awarded an EDCTP Senior
Fellowship. The longitudinal correlates studies focus
on correlates of risk of TB disease in various settings:
after BCG and novel vaccination against TB in infants,
after community-wide TB exposure in adolescents,
and after household exposure to a person with lung
disease in adults. Preliminary results point to marked
heterogeneity in mechanisms of risk of TB disease
and, secondly, to importance of inflammation. These
results have already challenged current paradigms in
TB pathogenesis.
The research of early- career scientists
GraemeMeintjes
and
Wendy Burgers
is focused at the intersection
of HIV and TB. Associate Professor Graeme Meintjes
is an infectious-diseases physician whose research
is targeted at improving understanding and clinical
management of conditions affecting patients with
advanced HIV disease. He was awarded a five-year
Wellcome Trust Intermediate Fellowship in 2012 that
will support a prospective cohort study of 660 patients
admitted to hospital with HIV-associated TB. This study
is aimed at defining contributors to the high mortality
in these patients and improving treatment strategies.
He is also principal investigator of a randomised
controlled trial of prednisone for the prevention of
the TB-associated immune reconstitution inflammatory
syndrome, a frequent complication occurring during
early antiretroviral therapy in patients with HIV and
TB. This trial is funded by an EDCTP Strategic Primer
Award made in 2012. Dr Wendy Burgers is a UCT
and University of Cambridge-trained immunologist
who holds a five-year Wellcome Trust Intermediate
Fellowship. She leads a growing research group of three
postdoctoral research fellows and four postgraduate
students, seeking to understand why HIV infection
leads to a greater susceptibility to TB. Also funded
by a Senior Fellowship Award from the EDCTP, her
work takes the unique perspective of attempting to
understand immunity to TB and the effect of HIV at
the site of disease, the lung. She is also principal
investigator on an NIH grant focusing on identifying the
mechanisms of excessive immune activation during HIV
infection, a process that drives progression to AIDS.
These studies could reveal important new targets for
immune intervention during HIV infection.