Scientists edge closer to beating world’s deadliest disease with first vaccine in over 100 years

Scientists may be on the verge of developing a new vaccine to combat tuberculosis (TB), one of the world’s deadliest diseases.

TB kills more than 1 million people each year and is especially fatal in developing countries where access to modern antibiotics is limited. The disease’s resistance to certain treatments has made respiratory infections the leading cause of infectious deaths worldwide.

More than a century ago, researchers developed the Bacillus Calmette-Guérin (BCG) vaccine, which significantly reduced TB cases in the United States from 80,000 annually to just a few hundred in subsequent years.

While the vaccine is effective for children, it is less protective in adults, especially in areas with high TB ​​prevalence.

Now scientists at the Massachusetts Institute of Technology (MIT) are working on a new generation vaccine using proteins produced by the Mycobacterium tuberculosis bacteria that causes tuberculosis.

The team infected human phagocytes, which are 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.

The researchers discovered that 24 peptides triggered a response from T cells, cells of the immune system that fight pathogens; This suggested that these peptides may help T cells recognize and destroy TB bacteria more effectively.

Although none of the peptides triggered a T-cell response in all cases, the team believes that a vaccine using a combination of them would likely work in most people.

Bryan Bryson, associate professor of biological engineering at MIT and fellow at the Ragon Mass General Brigham Institute in Boston, said: ‘There is still a huge burden of tuberculosis around the world that we want to have an impact on.

‘What we tried to do with this first TB vaccine was to focus on antigens that we often see on our screen and that also appear to stimulate a response in the T cells of people who have had previous TB infection.’

Today, tuberculosis infects several thousand Americans and kills about 500 each year; This number is much less than cancer, heart disease and dementia. But the threat is much more widespread in developing countries, and tuberculosis kills 1.2 million people worldwide each year.

Tuberculosis in the United States experienced a steady decline from 1993 to 2020, when the total number of cases reached an all-time low of 7,170. However, in 2021, this number increased to 7,866.

Since then, prevalence has increased every year.

The latest CDC data shows the United States provisionally records 10,347 TB cases in 2024, an eight percent increase from the previous year and the highest number since 2011, when there were 10,471 cases.

Cases are rising in 80 percent of US states, and experts attribute this to missed cases and distrust of doctors due to the Covid outbreak.

The demographics of tuberculosis also changed starting in 2001. This was the first year that the CDC reported more non-US-born patients with the disease than US-born patients; This meant that the driving force behind infections was immigrants and travellers.

All over the world, tuberculosis is prevented primarily by the BCG vaccine, which was developed in 1921. No other vaccines have been approved for use since then; This is largely because Mycobacterium tuberculosis produces more than 4,000 proteins, making it difficult to identify those that trigger a strong immune response.

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

‘If we can answer this question, we can design vaccines accordingly.’

Because the risk of tuberculosis is low in the United States, BCG is not routinely administered except in children who regularly come into contact with people with active tuberculosis or in healthcare workers in high-risk areas.

Where administered, it provides stronger protection in children than in adults.

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

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

They found that 27 TB peptides from 13 of the most frequently presented proteins were 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.

But none of the peptides worked in every donor.

Bryson said: ‘In a perfect world, if you were designing a vaccine you would choose a protein presented in each donor.

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

The team now has a mixture of eight proteins believed to protect most people against tuberculosis, and they continue to test this combination with blood samples from donors around the world.

They are also planning additional studies on animals, as human trials are likely several years away.

TB spreads through droplets released into the air when a person with active TB coughs, sneezes, or talks. Early symptoms include a persistent cough, sometimes bloody, chest pain, unexplained weight loss, fever, night sweats and loss of appetite.

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

Tuberculosis of the brain, also known as tuberculous meningitis, can damage vital tissues, increase intracranial pressure, and kill nerve cells, potentially leading to paralysis or paralysis. Deaths mostly result from respiratory failure due to bacterial damage to the lungs.