Scientists Found New TB Vaccine Targets That Could Save Millions

MIT biological engineers found new targets for a better tuberculosis vaccine. They identified specific antigens that may trigger stronger immune responses. These findings could lead to vaccine candidates that protect more effectively. Tuberculosis remains the world’s deadliest infectious disease.

Researchers conducted a large-scale screen of TB proteins to find potential targets. The screening revealed multiple antigens suitable for new vaccine design. From over 4,000 bacterial proteins, scientists pinpointed several highly immunogenic peptides. These peptides caused powerful reactions from T-cells, which fight infections.

Currently, only one vaccine helps prevent tuberculosis. It is called BCG and was developed from a bacterium that infects cows with TB. The vaccine has been widely used in many regions of the world. However, its protection is limited, especially against pulmonary tuberculosis.

Tuberculosis kills over one million people each year worldwide. The MIT study could help improve vaccine effectiveness and reduce global deaths. By finding better targets for immune responses, scientists may soon create stronger TB vaccines.

How Did Researchers Find Better Vaccine Targets?

Researchers developed the BCG vaccine over a century ago. It remains the only existing vaccine for tuberculosis. This long gap explains why no new vaccines have yet emerged. Mycobacterium tuberculosis, the bacterium that causes TB, produces over 4,000 proteins. This makes it difficult to identify which proteins create helpful immune responses.

In this new study, researchers narrowed the range of possible vaccine targets. They focused on TB proteins found on the surface of infected human cells. Immune cells infected by TB display chopped-up bacterial proteins called peptides. These peptides appear on the cell’s surface through molecules called MHC proteins.

MHC, or major histocompatibility complex, molecules show these peptides to T cells. This process activates immune responses against infection. There are two main classes of MHC molecules. Class I MHCs activate killer T cells, while class II MHCs activate helper T cells. Human cells primarily respond to class II MHC proteins.

Each MHC II gene can appear in hundreds of different forms. Because of this variation, every person can have a unique set of MHC II molecules. These differences cause individuals to present different antigens in response to infection. By focusing on the peptides displayed by MHC molecules, researchers reduced thousands of TB proteins to a much smaller group.

This approach shows how the immune system naturally presents infection-related information. It also helps reveal which proteins are best suited for vaccine development. To test their idea, scientists infected human cells with TB. After three days, they collected MHC peptide complexes from the surface of these infected cells.

Using mass spectrometry, the researchers identified which specific peptides appeared. They found 27 TB peptides linked to MHC II immune responses. These peptides came from 13 different bacterial proteins, which often appeared in infected cells. To further evaluate them, scientists exposed donated T cells from people with prior TB infections.

In this test, 24 peptides generated no T cell response in some samples. None of the proteins created an effective immune response in every donor. However, combining several of these peptides could improve vaccine coverage. A single vaccine containing these peptides might protect most people against TB infection.

What Could Make This TB Vaccine More Effective?

Many peptides that could inform new TB vaccines come from one protein class. These are called type 7 secretion systems, or T7-SSs. The peptides identified in this study represent only a small fraction of what TB can produce. However, when narrowed to those that trigger MHC I or MHC II responses, T7-SSs stood out prominently.

ESXA and ESXB are two well-known T7-SS proteins. Bacteria use them to escape immune cell defenses. Together, ESXA and ESXB can pierce membranes that immune cells build to trap bacteria. By breaking through these barriers, the bacteria can continue to spread infection.

Researchers then created mRNA vaccines containing ESXB and ESXG protein sequences. Several prototypes were designed to target specific compartments in infected cells. In their experiments, vaccines that focused on lysosomes showed the strongest effects. Lysosomes are cell organelles that break down unwanted molecules and pathogens.

These lysosome-targeting vaccines caused a thousand times more MHCs to appear on cell surfaces. This made TB peptides much more visible to the immune system. The response improved even more when ESXA was added to the formula. ESXA helped poke holes in lysosomal membranes, increasing antigen presentation.

The current vaccine mix contains eight proteins to offer broad TB protection. This formula could improve immune responses for most people worldwide. Still, many animal and human tests must take place before clinical trials begin. Researchers believe this work marks a crucial step toward better tuberculosis vaccines.

Conclusion

This study marks major progress toward creating a stronger tuberculosis vaccine. Researchers identified key TB proteins that trigger powerful immune responses in human cells. Their findings could lead to safer, more effective vaccines that protect millions worldwide.

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Logan Hamilton is a health and wellness freelance writer for hire. He’s passionate about crafting crystal-clear, captivating, and credible content that elevates brands and establishes trust. When not writing, Logan can be found hiking, sticking his nose in bizarre books, or playing drums in a local rock band. Find him at loganjameshamilton.com.