There’s exciting news on the horizon her. Researchers at MIT are potentially on the brink of launching a new vaccine that could take on tuberculosis (TB), which sadly remains one of the deadliest diseases out there.
Every year, TB claims more than 1 million lives worldwide, and it’s particularly devastating in poorer countries where modern antibiotics are hard to come by. This so-called superbug’s ability to outsmart treatments has positioned respiratory infections as the leading cause of death from infectious diseases, impacting countless lives.
Going back over a hundred years, the Bacillus Calmette-Guérin (BCG) vaccine has been our main defense against TB. It truly worked miracles, slashing annual TB cases in the U.S. from 80,000 to a mere few hundred in the years that followed the introduction of this vaccine.
However, while BCG works wonders for kids, its potency diminishes significantly in adults, especially in areas where TB runs rampant.
So what’s next? The MIT team is hard at work on a next-gen vaccine that leverages proteins made by the Mycobacterium tuberculosis, the bacteria behind TB.
To test their approach, they infected specific immune cells, known as human phagocytes, with M. tuberculosis, allowing these cells to consume and battle the bacteria. They then isolated MHC-II proteins from these cells and pinpointed certain peptides—short amino acid sequences—that work well with these proteins.
From this study, the researchers discovered 24 peptides that could effectively trigger a response from T cells, which are essential in our immune system’s fight against infections. This indicates that these peptides might dial up the ability of T cells to spot and destroy TB bacteria.
While it’s noteworthy that no single peptide generated a T cell response in every single case, the scientists are optimistic that combining these would be beneficial for most people.
Bryan Bryson, an associate professor at MIT, emphasized: “The TB crisis is a major concern globally, and we want to make sure we can offer help.”
He added, “Our goal with this initial vaccine is to zero in on frequently spotted antigens that seem to stimulate T cell activity, especially in people who have had previous TB infections.”
These days, a handful of TB cases surface yearly in the U.S., with about 500 fatalities, which is still minor compared to the likes of cancer or heart disease. Yet the bigger threat is in developing nations where the disease claims about 1.2 million lives annually.
TB cases in America were on a good downward trend from 1993 until 2020, hitting a historical low of 7,170 cases. But just a year later, numbers took a turn and reached 7,866.
It seems the trend continues upward, with the latest CDC data reporting that the U.S. saw 10,347 was logged in 2024, marking an 8% increase from the previous year and the highest figure since 2011.
Moreover, TB cases are surging in over 80% of U.S. states, attributed to missed diagnoses and a lack of trust in medical professionals fostered during the Covid pandemic.
Shifting demographics are also notable—the CDC indicated that since 2001, more TB infections are traced back to non-U.S.-born citizens, with international travelers and immigrants fueling a new wave.
Globally, the primary shield against TB has been the BCG vaccine from 1921. Surprisingly, we haven’t seen any new vaccines in the last century mainly because Mycobacterium tuberculosis creates more than 4,000 different proteins, complicating the quest for those that can effectively trigger a robust immune response.
What’s the strategy now? Bryson shared: “Instead of diving into all 4,000 TB proteins, we pivoted our focus on which ones are actually displayed to the immune system by MHC proteins. By understanding this, we hope to tailor effective vaccines efficiently.”
Given the low TB risk in the U.S., BCG isn’t routinely administered here, only offered to certain risk groups like children frequently exposed to TB or healthcare workers in at-risk roles.
Where it is administered, BCG is much stronger in kids compared to adult immunity.
A recent study published in Science Translational Medicine found that after infecting human phagocytes with Mycobacterium tuberculosis, they managed to isolate MHC-peptide complexes three days later. This highlighted promising vaccine targets by showcasing bits of TB proteins to T cells.
The scientists discovered that 27 peptides from 13 proteins were routinely presented. When T cells donated from individuals with previous TB exposure were tested, it turned out 24 of those peptides could evoke a reaction among at least some participants.
However, they noted not every peptide activated the T cells across all donors. Bryson pointed out: “Ideally, the perfect vaccine would feature one protein that works well for everyone. Regrettably, our tests haven’t yielded a universal TB protein just yet.”
As of now, the research team is focusing on a blend of eight proteins that they believe could give protection against TB for the majority and are persistently testing this combination with blood samples from around the globe.
Animal trials are on the agenda next, as human testing is projected to take a few more years to get started.
For anyone unsure, remember that TB spreads through the air from someone who coughs, sneezes, or even talks. Early warnings include symptoms like a persistent cough, possible blood, chest discomfort, unexpected weight loss, fever, night sweats, and reduced appetite.
As the disease progresses, patients may find it difficult to breathe and experience considerable lung damage. The bacteria can even spread to other vital organs like the brain and spine.
Infected brain tissue, known as tuberculous meningitis, can impair crucial functions, increasing skull pressure, harming nerve cells, and leading to conditions like paralysis or strokes. Unfortunately, respiratory failure from lung damage is a typical cause of death.
