Synthetic TB Vaccine Strategy Found Effective in Mice

Australian researchers from the Centenary Institute and the University of Sydney announced they have developed and tested a new type of vaccine candidate targeting tuberculosis (TB), the world's top infectious disease killer.

After 5-years of study, this advanced synthetic vaccine demonstrated its effectiveness against TB using mouse models, said these researchers in a press release on August 23, 2019.

"Tuberculosis is a huge worldwide health problem. It's caused by a bacteria that infects the lungs after it's inhaled, is contagious and results in approximately 1.6 million deaths per year globally," said Dr. Anneliese Ashhurst, co-lead author of the reported study and affiliated with both the Centenary Institute and the University of Sydney.

"Two peptides (small proteins) which are normally found in tuberculosis bacteria were synthesized and then bound extremely tightly to an adjuvant (a stimulant) that was able to kick-start the immune response in the lungs," said Dr. Ashhurst.

This study used immunogenic epitopes, ESAT61–20 and TB10.43–11 from Mycobacterium tuberculosis, which were covalently conjugated to the TLR2-ligand Pam2Cys to generate a self-adjuvanting lipopeptide vaccine. 

"We were then able to show that when this vaccine was inhaled into the lungs, it stimulated the type of T cells known to protect against TB.” 

“Importantly, we then demonstrated that this type of vaccine could successfully protect against experimental airborne TB infection," she said.

Professor Warwick Britton, Head of the Centenary Institute Tuberculosis Research Program and co-senior researcher on the project with Professor Richard Payne, School of Chemistry, University of Sydney, emphasized the importance of the work being done.

Bacille Calmette-Guérin (BCG) is a vaccine for TB. This vaccine is not widely used in the USA, but it is often given to infants and small children in other countries where TB is common.

There are an estimated 2 billion individuals carrying TB globally and up to 15 percent of these individuals develop the disease in their lifetime, says the World Health Organization (WHO).

Moreover, about 50 percent of TB cases occur in the Asia Pacific region.

Professor Britton is excited that the team's vaccine strategy - directly generating immunity in the lungs - has proven to be the right research approach to take.

"BCG fails to prevent infection or provide long term protection in older individuals and it isn't considered suitable for use in individuals with an impaired immune system. More effective vaccines are urgently required to save lives,” Professor Britton said.

"The important thing is that the vaccine actually gets to the lungs because that's where you first see TB.” 

“Ultimately, we would love to see a form of this vaccine available for use in an easily inhaled nasal spray which would provide life-long TB protection. Although this outcome is still many years away, we are certainly heading in the right direction.”

Our next steps will be to determine if our synthetic vaccine can be developed into a form suitable for use in humans," said Britton.