Boosting the power of the tuberculosis vaccine

22 January 2025

The BCG vaccine (Bacillus Calmette-Guerin) has been the only available tuberculosis vaccine for more than a hundred years. AITHM’s Dr Guangzu Zhao and Associate Professor Andreas Kupz are now working on a new type of vaccine that aims to boost the power of BCG, as BCG currently only protects children, but has limited efficacy against tuberculosis in adults.

“Australia has limited tuberculosis cases. Predominantly, because of our high living standards, good nutrition and small household sizes,” Associate Professor Andreas Kupz said. “But the situation is quite different when it comes to Australia’s nearest neighbours, Papua New Guinea (PNG) and Indonesia. These countries have some of the highest numbers of tuberculosis cases in the world.”

Vaccinating children in less developed areas of these countries can be a difficult task, as the BCG vaccine has to be constantly refrigerated between 2°C and 8°C and needs to be kept away from sunlight. This can be difficult when no permanent power supply is available. However, for now, there are no alternatives to BCG.

“Tuberculosis is a complex disease, and we don't seem to be able to find a vaccine that is better than BCG,” Associate Professor Kupz said. “Researchers have looked into the three possible vaccine types: the first one would be a preventative vaccine, that is, a replacement for BCG. The second type is a therapeutic vaccine, something that you would give to someone who already has tuberculosis.

“Our team is now working on the third type, on what we call a booster vaccine. For now, we think the best strategy is to make BCG even better by boosting the immune response BCG already elicits.”

The booster project team is led by Associate Professor Kupz and Dr Guangzu Zhao. “I was brought on board for my specific expertise; Associate Professor Kupz, for example, is an immunologist, and I am a biochemist,” Dr Zhao said.

“Before I started working on this project three years ago, I had worked on a peptide-based vaccine against Group A streptococcus (GAS),” Dr Zhao said. “GAS is responsible for a variety of mild infections as well as for life-threatening autoimmune diseases, such as rheumatic fever and rheumatic heart disease.”

Now Dr Zhao is using the same technique in the fight against tuberculosis. “Peptides and peptide epitopes are the basis of our booster. Peptides are small pieces of proteins, whereas peptide epitopes are a certain fragment of protein that are recognized by the immune system,” Dr Zhao said.

“Peptides alone are not able to induce a strong enough immune response. This is why our strategy is to prepare a vaccine using peptide epitopes and other peptide moieties (fragments),” Dr Zhao said. “When mixed into water, for example, our peptide vaccine can self-assemble spontaneously into nanoparticles. Nanoparticles are so small, they can only be seen in an electron microscope. This is why we are also calling our booster a ‘nanovaccine’,” Dr Zhao said.

“The strength of our booster nanovaccine is its simplicity,” Dr Zhao said. “Another advantage is that it is cold-chain independent. It doesn't have to be stored in a fridge or a freezer, it can be stored at room temperature.”

“At the same time, it’s flexible, it's a bit like a Lego system. Our nanovaccine is composed of six peptides, and each of the six peptides is one building block,” Associate Professor Kupz said. “Depending on the population you are treating, the six peptides might be enough, or we may need a modified selection, or potentially include other peptides.”

The AITHM’s nanovaccine was recently selected for a global head-to-head comparison by the Tuberculosis Vaccine Initiative (TBVI). TBVI supports the development of new, safe and effective tuberculosis vaccines that are accessible and affordable for all people.

“Our booster is one of six candidates that were accepted in late 2024. TBVI will use an independent lab to compare all six vaccine candidates,” Associate Professor Kupz said. “In our own trials, we have seen a good immune response, and we are confident that our nanovaccine will do very well in the TBVI trials as well.”

If successful, the AITHM team’s booster could become a game changer in the global fight against tuberculosis, offering new hope to millions of people worldwide.