30 April 2026 – Wits University
New ways of generating vaccines for tuberculosis using mRNA technology.
It’s the 2026 African Vaccination Week in SA from 24-30 April, and the global imperative to develop a more effective tuberculosis (TB) vaccine has intensified over the past few years. However, none have yet fully outsmarted the clever and adaptable TB bacterium, which remains a major health threat across Africa.
New vaccine approaches that generate strong tissue-resident memory T-cell immunity in the lungs could, however, prove to be a game changer.
These specialised immune cells remain in tissues such as the lungs rather than circulating through the bloodstream. Acting as local sentinels, they may recognise infection early and trigger a rapid immune response before the bacteria spread.
Scientists led by Dr Kristie Bloom at the Wits Antiviral Gene Therapy Research Unit (AGTRU) are exploring how next-generation mRNA vaccines could help stimulate tissue-resident memory T-cells.
“Our project is looking at new ways of generating vaccines for TB using mRNA technology,” says Bloom. “We are particularly interested in improving T-cell responses because they play a critical role in controlling tuberculosis infection.”
Bloom recently presented the team’s latest findings at an international conference in Belgium on next-generation mRNA vaccines against complex pathogens.
Vaccine development can take many years, with early discovery phases often lasting between two and five years. “But compared with many other products in the field, this project is moving relatively quickly,” Bloom notes.
Unlike many traditional vaccines that mainly stimulate antibody responses, mRNA vaccines instruct the body’s own cells to briefly produce a harmless piece of the pathogen. Because this antigen is produced inside cells, mimicking aspects of real infection, the immune system often generates strong cellular responses, including T-cell activity.
An urgent global health challenge
Tuberculosis remains one of the world’s deadliest infectious diseases. Globally, more than 10 million people develop TB each year, and the disease continues to claim over a million lives annually.
South Africa carries one of the highest TB burdens worldwide. An estimated 249,000 people developed TB in 2024, and around 54,000 died from the disease, underscoring the urgent need for improved prevention strategies.
While the Bacillus Calmette–Guérin (BCG) vaccine has been used for more than a century to protect infants against severe forms of TB, its protection against pulmonary TB in adolescents and adults – the form responsible for most transmission – is inconsistent.
The promise of mRNA technology
Messenger RNA (mRNA) vaccines gained global attention during the Covid-19 pandemic because they can be designed and manufactured far more rapidly than traditional vaccines.
Instead of delivering weakened pathogens or purified proteins, mRNA vaccines provide cells with temporary genetic instructions to produce a harmless piece of a pathogen known as an antigen. This trains the immune system to recognise and fight the real infection.
The instructions are packaged inside lipid nanoparticles, which are microscopic protective particles that help deliver the mRNA into cells.
Bloom’s team is exploring how this platform can be adapted for tuberculosis, a disease that has evolved sophisticated mechanisms to evade the immune system. “If we can position immune cells in the lungs that recognise TB early, we may be able to stop infection before it becomes established.”
The researchers are also investigating novel lipid nanoparticle formulations that could help direct vaccines to specific tissues. This approach has broader applications in infectious diseases and targeted therapies.
Moving toward clinical development
The AGTRU TB vaccine project has been under development for about three years and has already shown encouraging results in early experimental models.
“The mRNA vaccines have demonstrated T-cell responses and protection in mice,” says Bloom. The next step will involve toxicity studies and further optimisation of the vaccine formulation.
A global network of collaborations
The research is supported by an international network of collaborators, which enables the vaccine candidate to be tested in specialised laboratories around the world.
In South Africa, AGTRU works closely with the South African Tuberculosis Vaccine Initiative (SATVI) at the University of Cape Town, which brings extensive expertise in clinical TB vaccine research.
The researchers also collaborate with partners who operate high-containment laboratories needed to study tuberculosis infection.
International partners include scientists at Seattle Children’s Hospital in the United States, who use an ultra-low-dose infection model that mimics how people typically become infected, often through inhaling just one or two bacteria. Another partner is the Institut de Pharmacologie et de Biologie Structurale (IPBS) in Toulouse, France, part of the CNRS research network, which tests vaccine candidates in alternative animal models.
Building vaccine innovation in Africa
Bloom hopes the work will contribute to a growing pipeline of vaccines that can be developed and manufactured on African soil. “We want to contribute to locally developed vaccines. TB remains a major burden in South Africa and across the continent, so solutions developed here are incredibly important.”
As the search continues for the immune blueprint that can defeat tuberculosis, emerging platforms such as mRNA may provide a powerful new tool in the fight against one of humanity’s oldest diseases.