Tuberculosis kills around 1.3 million people every year, more than any other infectious disease. A central problem is not only the initial infection: TB bacteria can persist in a dormant state that survives antibiotics. When these so-called persisters reactivate, the disease breaks out again. Scientists at Johns Hopkins University published an unusual approach in the Journal of Clinical Investigation in April 2026: a vaccine against precisely these dormant forms, delivered through the nose.
The Problem of Sleeping Bacteria
Standard TB treatment consists of combinations of several antibiotics taken over six to nine months. They kill the actively growing bacteria, but a portion of tuberculosis organisms, known as persisters, switches into a metabolic standstill. In this state they are largely invulnerable to antibiotics. After treatment ends, they can reactivate and trigger a relapse. In drug-resistant tuberculosis, which does not respond to common antibiotics, the problem is compounded: the available reserve drugs are more expensive, more toxic, and less effective.
According to the WHO, there were 400,000 new cases of multidrug-resistant TB globally in 2023. Relapse rates after completed standard therapy range from five to twenty percent depending on the region.
How the Vaccine Works
The Johns Hopkins team led by researcher Styliani Karanika combined two genes in a single DNA construct: relMtb, a gene that helps TB bacteria maintain their dormant state, and Mip3α, an endogenous signalling protein that attracts immature dendritic cells. Dendritic cells are key players in the immune system: they take up antigens and activate the body's T-cell response.
By confronting the immune system with the persister gene, the vaccine trains the body to recognise and fight dormant tuberculosis bacteria, not just actively growing ones. Nasal delivery is not incidental: the airways are the primary route of TB infection. A vaccine acting via the nasal mucosa can, according to the researchers, generate a stronger local immune response exactly where it is needed.
What the Animal Trials Showed
Results from mouse trials, combined with standard TB therapy, were clear: faster elimination of bacteria from the lungs, less pneumonia, no relapse after treatment ended. Similar immune responses were observed in rhesus macaques, whose immune systems are closer to humans than those of mice. The vaccine worked both in combination with standard therapy and with the newer three-drug regimen of bedaquiline, pretomanid, and linezolid used against resistant TB.
The research group emphasises that the vaccine acts therapeutically, meaning in patients already infected, rather than preventively like a conventional vaccine. It therefore complements approaches such as the M72/AS01E candidate currently in a Phase 3 prevention trial.
Compared with the State of TB Control
The only licensed TB protection vaccine is the BCG vaccine, developed in 1921. It reliably protects infants against severe forms of the disease, but in adults its effectiveness is limited and in some regions near zero. Since BCG there has been no approved successor, despite more than a century of research.
The comparison makes the scale of the challenge concrete. Polio was reduced by 99.9 percent through consistent vaccination campaigns since 1988, according to the WHO. Hepatitis C, another chronic infectious disease that long had no cure, became curable in over 95 percent of patients from 2014 with direct-acting antiviral drugs. For tuberculosis, comparable breakthroughs have so far been absent. The length of treatment and the risk of relapse are the main reasons patients abandon therapy and resistances develop.
A nasal therapeutic vaccine that prevents relapses would intervene at exactly that point: it could help shorten therapy duration and slow the emergence of multidrug-resistant strains.
Three Hurdles to Human Use
Three steps separate the current results from clinical application. First: clinical trials. The animal results are promising, but there are many examples of vaccine candidates that worked in animal models and failed in humans. Phase 1 studies to assess safety and tolerability in people have yet to begin.
Second: production and cold chain. DNA vaccines place higher demands on storage and cold-chain logistics than conventional vaccines. For deployment in countries with the highest TB burden, including India, Indonesia, and Pakistan, a heat-stable formulation would be critical.
Third: financing clinical development. The Johns Hopkins researchers have demonstrated the underlying principle. Clinical development through to approval typically costs several hundred million dollars. For a disease that predominantly affects lower-income countries, commercial pharmaceutical interest is limited. Public funding through the Wellcome Trust or the Gates Foundation, together with procurement guarantees from the WHO, are considered the most likely route to financing.