Scientists develop Nasal DNA vaccine for tuberculosis

A new intranasal therapeutic vaccine against tuberculosis (TB), developed by researchers at Johns Hopkins University, has been shown in mice to clear bacteria more quickly, reduce lung inflammation, and prevent disease relapse when combined with first-line TB drug therapy.

The experimental vaccine, delivered through the nose, targets one of tuberculosis’s most persistent defenses: the bacteria’s ability to survive despite treatment.

In a study published in the Journal of Clinical Investigation, the vaccine combines two genes, relMtb and Mip3α, designed to train the immune system to target drug-tolerant bacterial “persisters.” These persisters can survive long courses of antibiotics and often lead to disease relapse.

According to the World Health Organisation (WHO), about one-quarter of the global population—roughly 2 billion people, carry latent TB infection without symptoms. In 2024, more than 10 million people developed active TB, and 1.2 million died from the disease, making it the leading cause of death from a single infectious disease.

Current TB treatment often requires lengthy multidrug regimens that can be difficult to complete, while drug-resistant strains continue to spread. The new vaccine developed at Johns Hopkins may help address these challenges.

In mouse studies, the vaccine increased the recruitment and activation of dendritic cells and enhanced their interaction with T cells in the lungs. It also produced strong, long-lasting immune responses both locally in the lungs and throughout the body, involving CD4 (helper T cells) and CD8 (killer T cells).

ALSO READ: Oyo govt confirms Lassa fever case, activates emergency response

In rhesus macaques, the intranasal DNA vaccine triggered measurable TB-specific immune responses in both the bloodstream and the airways. These responses were similar to those associated with reduced bacterial levels in mice. The immune activity lasted at least six months, suggesting the vaccine’s effects may be durable.

The researchers said their findings support a broader strategy that targets TB persisters through immunotherapy, rather than relying solely on antibiotics to kill actively growing bacteria. DNA vaccines are relatively stable and can be produced efficiently, which could make them practical if this approach proves successful in humans.

Study lead author Styliani Karanika, an assistant professor of medicine at the Johns Hopkins University School of Medicine, explained that when administered alongside first-line TB drug therapy, the intranasal DNA fusion vaccine helped infected mice clear the bacteria more quickly, reduced lung inflammation, and prevented relapse after treatment ended.

“The vaccine also enhanced the effectiveness of the TB drug combination of bedaquiline, pretomanid, and linezolid,” Karanika said, “suggesting it could be used alongside treatments for drug-resistant TB to help the body fight the disease, even in hard-to-treat cases.”