Scientists are on the brink of creating a groundbreaking vaccine to tackle tuberculosis (TB), one of the most lethal diseases worldwide.

Each year, TB claims over a million lives, with its impact most severe in developing nations where access to modern antibiotics is scarce. The disease’s growing resistance to current treatments has positioned respiratory infections as the top cause of infectious deaths globally.

Over a century ago, the Bacillus Calmette-Guérin (BCG) vaccine was developed, which significantly reduced TB cases in the United States from more than 80,000 annually to just a few hundred over the years. However, while the BCG vaccine is effective in children, its protective benefits diminish in adults, particularly in areas with high rates of TB.

Now, researchers at the Massachusetts Institute of Technology (MIT) are pioneering a next-generation vaccine. This new approach utilizes proteins from Mycobacterium tuberculosis, the bacterium responsible for TB.

The MIT team has been experimenting by infecting human phagocytes—white blood cells that enhance immunity by consuming and destroying harmful pathogens—with M. tuberculosis.

The team infected human phagocytes, white blood cells that boost immunity by engulfing and destroying pathogens, with M. tuberculosis. 

They then extracted MHC-II proteins from the surface of these cells and identified specific peptides, short chains of amino acids, that bind to these proteins. 

Researchers discovered that 24 peptides triggered a response from T cells, the immune system’s pathogen-fighting cells, suggesting these peptides could help T cells recognize and destroy TB bacteria more effectively. 

Researchers at MIT are working on a potential vaccine for tuberculosis, the world’s deadliest disease (stock image)

While none of the peptides triggered a T cell response in every case, the team believes a vaccine using a combination of them would likely work for most people.

Bryan Bryson, an associate professor of biological engineering at MIT and a member of the Ragon Institute of Mass General Brigham in Boston, said: ‘There’s still a huge TB burden globally that we’d like to make an impact on.

‘What we’ve tried to do in this initial TB vaccine is focus on antigens that we saw frequently in our screen and also appear to stimulate a response in T cells from people with prior TB infection.’ 

Today, TB infects a few thousand Americans every year and kills around 500, far fewer than cancer, heart disease and dementia. But the threat is much more prevalent in developing countries, however, and TB kills 1.2million people worldwide each year.

TB in the US was on a steady decline from 1993 until 2020, when the overall number of cases hit an all-time low of 7,170. But in 2021, that number jumped to 7,866.

Prevalence has gone up every year since. 

The latest CDC data shows the US provisionally recorded 10,347 TB cases in 2024, up eight percent from the year before and the highest tally since 2011, when there were 10,471 cases. 

Cases are now on the rise in 80 percent of US states, which experts have blamed on missed cases and distrust of doctors forged by the Covid pandemic.   

The demographics of TB have also shifted, starting in 2001. That was the first year the CDC reported more non-US-born citizen patients than US-born, meaning immigrants and travelers were the driving force behind infections. 

TB around the world is primarily prevented with the BCG vaccine, developed in 1921. Since then, no other vaccines have been approved for use, largely because Mycobacterium tuberculosis produces more than 4,000 proteins, making it difficult to identify those that trigger a strong immune response. 

Bryan Bryson, an associate professor of biological engineering at MIT, said: ‘Instead of looking at all of those 4,000 TB proteins, we wanted to ask which of those proteins actually end up being displayed to the rest of the immune system via MHC proteins. 

‘If we could answer that question, then we could design vaccines to match that.’ 

Because the risk of TB in the US is low, BCG is not routinely administered, except for children regularly exposed to people with active TB or for healthcare workers in high-risk areas. 

Where it is given, it provides stronger protection in children than in adults. 

In a study published this week in Science Translational Medicine, the researchers infected human phagocytes with Mycobacterium tuberculosis and, three days later, extracted MHC-peptide complexes from the cell surfaces. 

These complexes display fragments of TB proteins to T cells, helping researchers identify promising vaccine targets. 

They found that 27 TB peptides from 13 proteins were most frequently presented, and when exposed to T cells collected from blood samples donated by people previously infected with TB, 24 peptides triggered a response in at least some donors. 

However, none of the peptides worked for every donor. 

Bryson said: ‘In a perfect world, if you were designing a vaccine, you would pick one protein that is presented across every donor. 

‘It should work for everyone. However, using our measurements, we’ve not yet found a TB protein that covers every donor we’ve analyzed so far.’

The team currently has a mix of eight proteins they believe could protect against TB for most people, and they are continuing to test the combination with blood samples from donors around the world. 

They also plan additional studies in animals, as human trials are likely several years away.

TB spreads through airborne droplets released when a person with active TB coughs, sneezes, or speaks. Early symptoms include a persistent cough, sometimes coughing up blood, chest pain, unexplained weight loss, fever, night sweats, and loss of appetite.

In later stages, patients may experience severe breathing difficulties and extensive lung damage, and the infection can spread to other organs, including the brain and spine. 

TB in the brain, also known as tuberculous meningitis, can damage vital tissues, increase intracranial pressure, and kill nerve cells, potentially leading to paralysis or strokes. Deaths are most often caused by respiratory failure due to bacterial damage to the lungs.