Research & Innovation 2015-16 - Page 60

Biomarker discovery offers hope for
new TB vaccine development
A team of scientists from UCT, Oxford University and the London School of
Hygiene and Tropical Medicine have made a discovery that reveals how we
can improve development of more effective vaccines against TB.
TB is the biggest killer of humans due to bacterial
infection. In 2014, 9.6 million people were diagnosed
with TB, and 1.5 million died. The only available vaccine
against TB, BCG, is given to infants to prevent severe
forms of the disease; but protection against lung disease
is very variable – particularly in countries where TB is
most common, such as South Africa.
The research team studied young children who had
previously participated in a large clinical trial of a new
TB vaccine conducted in Worcester, in the Western
Cape. They investigated the immune response to BCG,
given at birth, to determine the characteristics of this
response that are associated with protective immunity
against TB. “We looked at a number of factors that
could be used as immune correlates, to try and find
biomarkers that will help us develop a better vaccine,”
said Professor Helen McShane of Oxford University,
who led the study. The team carried out tests for 22
immune-response characteristics, and found that
elevated activation of CD4 T cells was linked to higher
TB disease risk. Higher levels of T cells, that responded
to the BCG vaccine by producing IFN, the immune
messenger molecule, were linked to reduced risk of TB.
Antibodies to the Ag85A protein made by the TB
bacterium were also identified as a possible immune
correlate. Higher levels of antibodies targeted against
Ag85A were associated with lower TB risk. However,
the team cautions that other environmental and
disease factors could also cause Ag85A antibody
levels to rise, and so there may not be a direct link
between these antibodies and TB risk.
TB is an international killer
Professor McShane said: “These are useful results, which
ideally would now be confirmed in further trials. They show
that antigen-specific T cells are important in protection
against TB, but that activated T cells increase the risk.”
Associate Professor Tom Scriba, from the South African
Tuberculosis Vaccine Initiative (SATVI) at UCT, said: “TB
is still a major international killer, and rates of TB disease
in some areas of South Africa are among the highest in
the world. These findings provide important clues about
the type of immunity TB vaccines should elicit, and
bring us closer to our vision – a world without TB.”

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