The Breakthrough

Researchers at Johns Hopkins Medicine and the Johns Hopkins Bloomberg School of Public Health have developed an experimental therapeutic DNA vaccine for tuberculosis (TB) that is delivered through the nose. The vaccine targets drug-tolerant TB bacteria known as "persisters," which can survive lengthy antibiotic treatment and trigger relapse.

The findings were published in the Journal of Clinical Investigation.

The Scale of the Problem

Tuberculosis has afflicted humans for at least 6,000 years and remains one of the world's deadliest infectious diseases. According to the WHO: - Roughly one-quarter of the global population — about 2 billion people — carry latent TB infections without symptoms - In 2024, more than 10 million people developed active TB - 1.2 million died from the disease, making it the leading cause of death from a single infectious pathogen

How It Works

The vaccine combines two genes — relMtb and Mip3α — and is administered through the nose to take advantage of several biological mechanisms:

1. Targeting persisters: The relMtb gene produces a protein that helps TB bacteria survive hostile conditions by entering a drug-tolerant persistent state 2. Immune recruitment: Fusing relMtb with Mip3α attracts immature dendritic cells, which present TB proteins to T cells 3. Respiratory focus: Intranasal delivery concentrates immune activity where TB infections begin — the respiratory mucosa in the lungs

Results

In mouse experiments, the vaccine: - Increased recruitment and activation of dendritic cells - Generated durable T-cell responses from both CD4 (helper) and CD8 (killer) cells - Cleared infections faster when combined with first-line drug therapy - Reduced lung inflammation - Prevented relapse after treatment ended - Enhanced the powerful drug combination of bedaquiline, pretomanid, and linezolid against drug-resistant TB

In rhesus macaques, the vaccine generated measurable TB-specific immune responses in both the bloodstream and airways lasting at least six months.

What's Next

Additional research is required before the vaccine can advance to human clinical trials. However, because DNA vaccines are generally stable and can be produced efficiently, the approach could offer practical advantages if future studies confirm the benefits in humans.

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