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Researchers could be nearing the development of a novel vaccine to fight tuberculosis (TB), a disease responsible for numerous fatalities worldwide.

TB causes the death of over 1 million people annuallyand is especially dangerous in developing nations where availability of advanced antibiotics is restricted. The illness’s ability to resist specific therapies has led to respiratory infections becoming the top cause of infectious-related deaths worldwide.

Over a hundred years ago, scientists created the Bacillus Calmette-Guérin (BCG) vaccine, which significantly lowered the number of TB cases in the US, from more than 80,000 each year to just a few hundred in the subsequent decades.

Although it works well for children, the vaccine offers reduced protection for adults, particularly in areas where tuberculosis is common.

Now, scientists at the MassachusettsThe Massachusetts Institute of Technology (MIT) is developing a new generation of vaccines that utilize proteins generated by Mycobacterium tuberculosis, the bacterium responsible for tuberculosis.

The group infected human phagocytes, white blood cells responsible for enhancing immunity by ingesting and eliminating harmful agents, with M. tuberculosis.

They subsequently isolated MHC-II proteins from the cells’ surface and discovered particular peptides, which are brief sequences of amino acids, that attach to these proteins.

Scientists found that 24 peptides activated T cells, which are the immune system’s cells responsible for fighting pathogens, indicating these peptides may enable T cells to identify and eliminate TB bacteria more efficiently.

Although none of the peptides elicited a T cell response in all instances, the researchers think a vaccine combining them could probably be effective for the majority of individuals.

Bryan Bryson, an associate professor of biological engineering at MIT and a member of the Ragon Institute of Mass General Brigham in Boston, stated: ‘There remains a significant global burden of TB that we aim to have a meaningful effect on.’

We have aimed to concentrate on antigens that we frequently identified in our screening process and which also seem to trigger a response in T cells from individuals who have previously had TB.

Currently, tuberculosis affects several thousand Americans annually and results in approximately 500 deaths, which is much lower compared to cancer, heart disease, and dementia. However, the risk is significantly higher in developing nations, where TB claims the lives of 1.2 million people globally each year.

Tuberculosis in the United States saw a consistent decrease from 1993 up until 2020, when the total number of cases reached its lowest point at 7,170. However, in 2021, this figure increased to 7,866.

The rate has increased annually since then.

Recent CDC statistics indicate that the United States reported 10,347 tuberculosis cases in 2024, marking an eight percent increase from the previous year and the highest number since 2011, when 10,471 cases were documented.

More than 80 percent of U.S. states are experiencing an increase in cases, according to experts who attribute this trend to overlooked infections and a loss of confidence in medical professionals caused by the COVID-19 pandemic.

The composition of TB cases has also changed, beginning in 2001. That year marked the first time the CDC recorded more patients who were not born in the US compared to those who were, indicating that immigrants and travelers became the main contributors to infections.

Tuberculosis globally is mainly prevented through the BCG vaccine, which was created in 1921. Since that time, no additional vaccines have received approval, largely due to the fact that Mycobacterium tuberculosis contains over 4,000 proteins, complicating the identification of those that elicit a robust immune reaction.

Bryan Bryson, an associate professor in biological engineering at MIT, stated: ‘Rather than examining all 4,000 TB proteins, we aimed to determine which of these proteins are ultimately presented to the rest of the immune system through MHC proteins.’

If we were able to respond to that question, we could develop vaccines tailored accordingly.

Since the likelihood of tuberculosis in the United States is minimal, the BCG vaccine is not typically given, except to children who frequently come into contact with individuals having active TB or to healthcare professionals working in areas with a high risk.

Where applicable, it offers greater safeguarding for children compared to adults.

A study released this week in Science Translational Medicine involved infecting human phagocytes with Mycobacterium tuberculosis, and three days later, the scientists isolated MHC-peptide complexes from the cell surfaces.

These structures present parts of TB proteins to T cells, assisting scientists in discovering effective vaccine candidates.

They discovered that 27 TB peptides from 13 proteins were most commonly displayed, and when exposed to T cells gathered from blood samples provided by individuals who had previously been infected with TB, 24 of these peptides induced a reaction in at least a few donors.

However, no peptides were effective for all donors.

Bryson stated, “In an ideal scenario, if you were developing a vaccine, you would select one protein that is displayed by all donors.”

It should be effective for all individuals. Nevertheless, based on our measurements, we have not yet identified a TB protein that covers every donor we have examined to date.

The group currently has a combination of eight proteins that they think may offer protection against TB for the majority of individuals, and they are still evaluating the mixture using blood samples from donors across the globe.

They also intend to conduct further research on animals, as clinical trials on humans are expected to take several years.

Tuberculosis spreads via airborne particles that are released when an individual with active TB coughs, sneezes, or talks. Initial signs may consist of a long-lasting cough, occasionally involving the expectoration of blood, chest discomfort, unexpected weight reduction, fever, excessive night sweating, and a decreased desire to eat.

In advanced stages, individuals might face significant respiratory issues and widespread lung injury, with the infection potentially spreading to other organs such as the brain and spinal column.

Tuberculosis affecting the brain, referred to as tuberculous meningitis, can harm critical tissues, elevate pressure within the skull, and destroy nerve cells, possibly resulting in paralysis or strokes. Most fatalities occur due to respiratory failure caused by bacterial damage to the lungs.

Read more

• With the BCG vaccine no longer in use, could upcoming generations face a threat from the hidden spread of tuberculosis as more people remain unvaccinated?
• Has the increase in TB cases in the United States indicated the resurgence of this fearsome ancient disease amid the challenges of the 21st century?
• How are specialists linking the COVID-19 outbreak to the concerning increase in tuberculosis cases?
• Did a COVID vaccine booster trigger a fatal TB outbreak when a man’s immune system became unstable?
• Has tuberculosis become the world’s most lethal infectious disease, surpassing Covid-19 with 8.2 million cases reported in 2023?