Prof Warwick Britton

Australian researchers are a step closer to developing a more effective vaccine against tuberculosis based on a novel ‘pulmonary immunisation’ technique.

Scientists at the Centenary Institute in Sydney have demonstrated how an influenza-based vaccine can be used to activate CD4+ memory T cells in the lung that are associated with protection against tuberculosis.

The work is based on the premise that more effective protection against M. tuberculosis can be conferred by using intranasal immunisation methods to the lung rather than the traditional injection technique such as BCG vaccine.

In a study published in the scientific journal Mucosal Immunology, researchers identified lung parenchyma tissue-resident M. tuberculosis-specific CD4+ T cells that had been induced by recombinant influenza A viruses (rIAV) vaccines to express M. tuberculosis peptides. In further experiments, they showed that resident memory T cells were protective against tuberculosis independent of circulating memory T cells.

In animal models, they showed that mice immunised with the influenza-based vaccine were protected against M. tuberculosis infection even when circulating T cells were profoundly depleted.

“Therefore, pulmonary immunisation with the recombinant influenza A vaccine stimulates lung-resident CD4+memory T cells that are associated with early protection against tuberculosis infection,” they concluded.

And by stimulating memory T cells in the lung, a pulmonary vaccine could provide early protection in the lung, according to Head of Centenary’s Tuberculosis Research Program, Professor Warwick Britton.

“This research has been five years in the making. Previously TB vaccines were given by injection, but delivery of the vaccine to the lung may provide improved protection,” he said.

“In this study we proved that immunisation of the lungs with an Influenza-based vaccine stimulated memory T cells in the lungs that were able to protect against virulent TB infection. We are already using this breakthrough to develop other sub-unit vaccines, suitable for delivery to the lungs in humans,” said Professor Britton.

While Australia is a low-risk country for tuberculosis, the lung infection affects 10.4 million people globally a year and 1.7 million people die as a result.

Childhood BCG is effective against tuberculosis but its immunity wanes after about 15 years, meaning it is largely ineffective in adults.