Imma Perfetto
Cosmos science journalist
Biomedical scientists are urgently developing new vaccines to prevent tuberculosis (TB), the deadliest infectious disease in the world which kills about 1.5 million people each year, mostly in East Asia, Africa, and the Western Pacific.
While the disease is uncommon in Australia, Aboriginal and Torres Strait Islander people in the Northern Territory and Far North Queensland are disproportionally affected.
The only licenced TB vaccine, the Bacille Calmette-Guérin (BCG) vaccine, was developed a century ago. It protects children from serious forms of TB but its effectiveness is limited in adults.
Texas researchers are trialing a new approach and in tests on monkeys say their vaccine candidate provides much better protection, and triggers a superior immune response against TB infection, compared to BCG.
A live-attenuated TB vaccine, called delta sigH, is under development at Texas Biomedical Research Institute in the US. It is made of an attenuated or weakened strain of Mycobacterium tuberculosis (Mtb), the bacterium that causes TB.
A gene needed to make a protein called sigmaH is deleted, which makes the bacterium unable to survive in the lungs.
In 2015, the vaccine was shown to fully protect rhesus macaques (Macaca mulatta) against a lethal dose of Mtb, but how it did so was unclear. In a new Nature Communications study, researchers have now discovered it can also protect a different species of primate, and figured out how it does so.
“By analysing this in a different species, this shows it is not just a one-off and gives us more confidence the vaccine is likely to work in humans,” says Professor Deepak Kaushal, senior author of the paper.
Deepak and colleagues found that delta sigH recruited more B and T immune cells to the airways of the cynomolgus macaques (Macaca fascicularis) compared to the BCG. These cells are critical to how the immune system fights off infections.
Importantly, this did not result in excessive, harmful inflammation. Instead, delta sigH vaccination led to much lower levels of a protein (IDO) which is known to cause heightened inflammation and make it difficult for the immune system to combat TB.
Showing the mechanisms that provide this protection can inform next-generation TB vaccines.
But other key questions remain before delta sigH can be rolled out to the populations who need it most in low- and middle-income countries. These include how long the protection against TB lasts, and whether the vaccine is effective when delivered through injection, as opposed to directly to the lungs via aerosol as in this study.
Kaushal and his team are also working to develop and test versions of the delta sigH vaccine with more than one gene knocked out, so that it can be safely tested in humans.
“The next round of studies are underway,” says Kaushal.
“While we are still years away from seeing this vaccine in the clinic, these latest results are giving us more insight to fight this insidious disease.”
