Nasally Delivered DNA Vaccines for Tuberculosis: A New Frontier in Prevention and Treatment:

Tuberculosis (TB) is the leading cause of death in the United States as a single infectious and airborne disease that affects, but is not limited to, the lungs (World Health Organization, 2025). Though it is mostly asymptomatic and non-contagious, about 5-10% of individuals infected develop TB, with an increased risk in babies and young children. While it has traditionally been treated with antibiotics, the struggle to treat TB with drug-resistant solutions persists as long, multidrug courses are often difficult to complete (Centers for Disease Control and Prevention, 2024). To address this issue, a research team at Johns Hopkins Medicine and Johns Hopkins Bloomberg School of Public Health introduced their intranasal Deoxyribonucleic Acid (DNA) vaccine for tuberculosis on April 1, 2026.

Study Lead Author Styliani Karanika, an assistant professor of medicine at the Johns Hopkins University School of Medicine, revealed that the DNA vaccine fused two genes: relMtb and Mip3a (John Hopkins Medicine, 2026). These genes direct the immune system to fight drug-tolerant TB that can survive antibiotic therapy (Johns Hopkins Medicine, 2026). The TB bacteria uses the relMtb gene to produce a RelMtb protein that helps itself survive hostile conditions by entering a drug-tolerant persistent state (Dahl et al., 2003). The fusion of the relMtb gene and Mip3a gene produces a signal that attracts immature dendritic cells, which are critical in activating immune cells known as T cells to coordinate a response to the TB bacteria (Johns Hopkins Medicine, 2026).

The traditional, antibiotic-centered approach aims to disrupt processes such as DNA transcription, energy metabolism, and protein synthesis (Patsnap Synapse, 2025). However, even when antibiotics are effective, they only eliminate actively replicating bacteria. On the other hand, the DNA vaccine provides a promising approach to the treatment of TB, with its distinct benefits of cost-efficient production, safety in handling, and durability. With its intranasal injection, the vaccine focuses on the respiratory mucous membranes to generate long-lasting localized T-cell immunity in airways and lungs (Johns Hopkins Medicine, 2026). In a study on mice, the mice were treated daily with human-equivalent doses of oral drug-susceptible TB for a total of six weeks (Karanika et al., 2026). The results revealed that the IN Mip3a/relMtb fusion vaccine was the most effective compared to other controlled groups with increased dendritic cell recruitment and durable T-cell responses. With their study with rhesus macaques, a type of primate, Professor Karanika observed similar TB-focused immune responses in blood and airways, and results persisted for at least six months.

These studies were conducted on nonhuman primates. Moreover, the study results only measure the immune activation and not the subject’s response to TB challenges, which complicate the promises of this new treatment. Professor Karanika noted a few limitations of the research findings due to “a formal relapse analysis in this model” and “the lack of a benchmark therapeutic vaccine against which to compare the efficacy of the Mip3a/relMtb fusion vaccine” (Karanika et al., 2026). Currently, scientists need to conduct more research before the approval of human clinical trials.

Despite such drawbacks, the intranasal DNA vaccine remains to support a broader strategy of targeting TB with immunotherapy, which uses substances to help the immune system fight against cancer, infections, or any other disease (National Cancer Institute, 2019). Studies have also found that the vaccine performed more effectively alongside powerful TB drug combinations of bedaquiline, pretomanid and linezolid, suggesting that it may be helpful in pre-existing treatments for especially hard-to-treat cases (Johns Hopkins Medicine, 2026). Historically, the limited ability to provoke an immune response in nonhuman primates and humans of DNA vaccines has undermined their use (Karanika et al., 2026).

However, recent developments shed more light on their scientific value by revealing advancements in their safety and effectiveness, and given its practical benefits, scientists hope to implement this treatment in clinical trials soon.


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