
Johns Hopkins researchers have developed an intranasal DNA vaccine for tuberculosis that targets "persister" bacteria — the ones that hide from antibiotics and trigger relapses. In animal studies, the vaccine cleared infections faster, reduced lung inflammation, and even boosted the effectiveness of drugs used against drug-resistant TB. Human trials are still ahead, but early results are encouraging.
Tuberculosis kills over a million people every year, and one of the biggest reasons is a stubborn subset of bacteria called "persisters" — microbes that go dormant to survive antibiotic treatment and then reactivate later. Johns Hopkins researchers think they've found a new way to take them down: a DNA vaccine delivered through the nose.
The experimental vaccine combines two genes — relMtb and Mip3 — to attract immune cells directly to the lungs, where TB takes hold. By targeting the respiratory mucosa, it generates both local and systemic T-cell immunity. In mouse studies, it cleared bacteria faster, reduced lung inflammation, and prevented relapse after treatment. It also enhanced the effectiveness of a powerful drug combination used against drug-resistant TB. In rhesus macaques, the vaccine produced durable immune responses lasting at least six months — though the primate study assessed immune activation only, and did not test response to actual TB infection.
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Why it matters: Drug-resistant TB is a growing global crisis, and current treatment regimens are long, grueling, and often incomplete. A therapeutic vaccine that bolsters the immune system's ability to eliminate persistent bacteria — and enhances existing drug therapies — could be a meaningful step forward for millions of patients worldwide.