Australian researchers have modified the world’s only tuberculosis (TB) vaccine to produce stronger, longer-lasting protection in early trials, a development that could reshape how the disease is prevented in the future.
A major global challenge
TB is a bacterial infection caused by Mycobacterium tuberculosis. It remains a major challenge, claiming around 1.2 million lives globally each year.
BCG, the sole vaccine currently available, has been in use for more than a century, but experts say “its effectiveness varies”.
It reportedly works well in infants and young children against severe forms of TB, but its protection in adults is less reliable.
In response, a team from the Centenary Institute and the University of Sydney set out to re-engineer how the vaccine interacts with the immune system.
Their findings, published in the journal Vaccine, “found that modifying BCG to better target key immune cells improved the immune response generated by vaccination and provided longer-lasting protection against TB”.
“Our experiments showed that the modified BCG was taken up more effectively by dendritic cells [the immune system’s first responder] and stimulated greater immune activity, including a stronger response from T cells, with more T cells producing multiple immune signalling molecules,” says lead study author, Dr Claudio Counoupas from the Centenary Institute’s Centre for Infection and Immunity.
“Importantly, this enhanced immune response was associated with stronger protection against TB in the lungs, which was maintained for longer than the protection provided by standard BCG in our experimental model.”
A strong starting base
The researchers say the findings provide a strong basis for further investigation into ways to improve BCG and develop more effective TB vaccines.
“BCG has been used for more than 100 years, but there remains a need for new vaccines that can provide stronger and more sustained protection against TB,” says study senior author Professor Jamie Triccas from the University of Sydney.
“Our findings show that targeting BCG to dendritic cells can improve its protective efficacy in this preclinical model.
“While these findings are encouraging, we need to better understand whether this approach could ultimately translate into improved protection against TB in people.”
The team’s work to refine the modified vaccine is ongoing.
