Why new TB vaccines are urgently needed
Today is World Tuberculosis Day. Tuberculosis (TB) is still the deadliest infectious disease in the world: around 1.2 million people die from it each year. At BPRC, researchers are working on new vaccines that better protect against the most contagious form of TB. This is urgently needed, because the current vaccine falls short, especially for older people who can become seriously ill.
The vaccine we use worldwide is more than a hundred years old and mainly protects young children. But in adolescents and young adults, the group in which TB spreads the most, that protection declines sharply. “Around the age of 15 to 20, that protection is often already limited”, says a researcher at BPRC. “That group plays a major role in the spread of TB. That is why developing better vaccines and new vaccination strategies is urgently needed. Older people can also become seriously ill from TB”.
‘Other routes of administration may offer better protection’
The current vaccine was developed over a century ago and is based on a bacterial strain from cattle. It is administered through the skin. This works well against severe forms of TB in young children, such as meningitis, but does not provide sufficient long-term protection against pulmonary TB.
That is why researchers are looking at a different approach: vaccination directly via the lungs. The idea behind this is logical. “What we see is that other routes of administration, for example via the lungs, can provide stronger protection. This immune response arises locally in the lungs and is therefore difficult to detect in the blood, but appears to offer better protection against infection and disease progression”.
This could involve administering vaccines via a nebulizer, a kind of inhaler, so that the vaccine ends up directly in the airways. In the future, this could be easier to apply in practice than more complex methods. This approach is currently being studied, but has not yet been translated into clinical application.
A difficult disease to combat
Developing a new TB vaccine is more complicated than for many other infectious diseases. TB behaves differently from viruses such as coronavirus.
For example, the bacterium can remain ‘dormant’ in the body for years without causing symptoms. Only when the immune system is weakened can the disease become active. “In people with HIV, TB is for example the most important co-infection and a common cause of death”. In addition, it is often difficult to determine whether someone is infected, while that person can still transmit the disease.
The immune system also responds differently to TB. Whereas for many vaccines antibodies provide sufficient protection, in TB the cellular immune response plays a particularly important role. This makes the development of effective vaccines more complex. An additional challenge is that researchers do not yet have clear blood markers that predict whether someone is protected.
New vaccines in development
New vaccines are being developed worldwide. Some of these are already in clinical studies, but it takes a long time before it becomes clear whether they really work. This is because TB develops slowly and large-scale studies take many years.
In the meantime, scientists are investigating different strategies, such as booster vaccinations at a later age and new types of vaccines that better match the human variant of the bacterium. For example, a new vaccine is being tested that is based on the human TB bacterium instead of the current bovine variant. Previous studies also show that booster vaccination via the skin does not provide sufficient protection, which means new strategies are needed.
“It is really a difficult pathogen. This kind of research takes time, but the need is great”, says the researcher.
Why this research is important
To understand which vaccines really work, researchers need to be able to follow the entire process from vaccination to infection to protection. This cannot be done fully in the lab or with blood tests alone.
“That is exactly why research in a model that closely resembles humans is essential”, the researcher explains. “We therefore conduct research with macaques, because the course of the disease and the immune system are very similar to those of humans and vaccines affect the entire body. These kinds of complex responses can only be properly studied in a model that replicates the full system, because in vitro models do not fully reflect these responses. Only then can you see how the immune system in the lungs responds and whether a vaccine actually protects against infection and spread, something that cannot be directly tested in humans”.
The goal is clear: a vaccine is needed that not only protects young children, but also provides long-lasting protection against the contagious form of TB in adults. “Because as long as that protection is lacking, tuberculosis will continue to spread worldwide”.
