Apr 09, 2026
3 min read
In an article published today in the Journal of Clinical Investigation, a research team at Johns Hopkins Medicine and the Johns Hopkins Bloomberg School of Public Health reports that they are developing an intranasal (nasal) DNA vaccine against tuberculosis.
- In a paper published today in the Journal of Clinical Investigation, a team of researchers from Johns Hopkins Medicine and the Johns Hopkins Bloomberg School of Public Health reported developing a therapeutic intranasal (delivered through the nose) DNA vaccine against tuberculosis (TB) that combines two genes to direct the immune system to fight drug-tolerant, antibiotic-resistant bacteria, the long-term antibacterial-surviving bacteria.Treatment and lead to disease relapse.
Tuberculosis has been considered by the World Health Organization (WHO) for at least 6,000 years as a latent and undiagnosed disease for a quarter of the world's 2 billion people.In 2024 alone, the WHO says more than 10 million people worldwide have active TB disease, with 1.2 million deaths recorded.TB is the leading cause of death from infectious diseases alone.
In recent years, the WHO has recommended that there be therapeutic vaccines that can be used together with drugs to shorten the treatment of TB and improve the results, especially because the long course of many drugs is difficult to complete, and the types of TB that cannot be treated with drugs are constantly emerging.A drug described in a new Johns Hopkins study shows promise in meeting that need.
“Our intranasal DNA fusion vaccine, administered with first-line drug therapy for tuberculosis, helped infected mice clear disease bacteria more quickly, reduce lung inflammation, and prevent relapses after treatment ended,” says study lead author Styliani Karanika, M.D., faculty member of the Johns Hopkins Tuberculosis Research Center and assistant professor at Johns University School of Medicine."The vaccine also made the powerful anti-tuberculosis drug combination of bedaquiline, pretomanid and linezolid work better, suggesting it could be used in conjunction with drug-resistant tuberculosis treatments to help the body fight the disease, even in difficult-to-treat cases," Hopkins said.
The new Johns Hopkins vaccine fuses two genes, relMtb and Mip3α, and is given nasally to take advantage of three beneficial biological activities, Karanika said.
"First, TB bacteria contain the relMtb gene, which produces the RelMtb protein, which helps the bacteria survive adverse conditions such as antibiotic exposure, low oxygen, and nutrient limitation, entering a drug-resistant state."“Mixing relMtb with the Mip3α gene creates a signal that attracts immature dendritic cells—stem cells that take up TB proteins and deliver them to T cells."Presenting" immune cells that help coordinate a targeted attack by TB bacteria."
"Finally, intranasal administration concentrates the vaccine on the airway mucosa in the lungs where TB infection occurs, which helps generate long-term localized T-cell immunity in the airways and lungs, as well as a systemic immune response," says Karanika.
By combining these strategies, the researchers sought to increase immune system activity directly in the airways.In mouse studies, this approach increased the recruitment and activation of dendritic cells, improved the dense clustering of dendritic cells and T cells in the lung, and generated durable, antigen-stimulated T cell responses from two types of T cells, CD4 (also known as helper T cells) and CD8 (known as killer cells), both locally and systemically.
In rhesus macaques, the researchers found that their nasally administered DNA vaccine elicited measurable immune responses targeting tuberculosis in the blood and airways, similar to what led to fewer bacteria in the lungs of the mice they studied.These responses lasted at least six months, indicating the durability of the vaccine's effects.However, Karanika says, this primate work only measured immune activation, not a response to a tuberculosis challenge.
He says more studies are needed before any human clinical trials are approved.
"These data in non-human animals are encouraging because they show that the Mip3a/relMtb vaccine can generate a strong antigen-stimulated immune response in an animal model whose immune system closely resembles that of humans," said Karanika."This gives us an important bridge between the efficacy studies in mice and the additional clinical work needed before testing in humans."
The authors say their findings support a more comprehensive strategy to target TB, continuing with vaccination rather than relying solely on antibiotics to actively eradicate bacterial infections.Because DNA vaccines are stable and efficiently produced, they could offer significant benefits if this approach proves effective in humans.
Along with Karanika, the Johns Hopkins team of investigators includes Tianyin Wang, Addis Yilma, Jennie Ruelas Castillo, James Gordy, Hannah Bailey, Darla Quijada, Kaitlyn Fessler, Rokeya Tasneen, Elisa M. Rouse Salcido, Farah Shama, Harley Harris, Fengyixn, Chencoinia Zhang Alheng.Karantanos, Amanda Maxwell, Eric Nuermberger, J. David Peske, Richard Markham, and Petros Karakousis.
Federal funding for this study came from National Institutes of Health grants R01AI148710, K24AI143447, P30AI18436, K08AI174959, and P30CA006973.
Additional funding was provided by a Gilead HIV Research Scholar Award, a Johns Hopkins University Tuberculosis Development Center Award, a Johns Hopkins University AIDS Research Center HIV/AIDS Development Award, a Willowcroft Foundation Award, a Johns Hopkins University Clinical Scientist Award, and the Potts Memorial Foundation.
Karanika, Gordy, Markham, and Karakousis are the inventors of the anti-Mip3α/relMtb patent PCT/US2023/065584.None of the authors have any conflicting declarations of interest to report.
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Journal of Clinical Research R01AI148710, K24AI143447, P30AI18436, K08AI174959, P30CA006973
