Baltimore, USA, Apr 03: Researchers at Johns Hopkins Medicine and the Johns Hopkins Bloomberg School of Public Health have developed a novel intranasal DNA vaccine that could significantly improve treatment outcomes for tuberculosis (TB), one of the world’s deadliest infectious diseases. The findings were published in the Journal of Clinical Investigation.
The innovative vaccine is designed to be administered through the nose and works alongside standard drug therapies to enhance the body’s immune response against TB. It specifically targets drug-tolerant bacterial “persisters,” which are known to survive prolonged antibiotic treatment and contribute to disease relapse.
According to the World Health Organization, TB remains a global health crisis, with approximately 2 billion people carrying latent infections and more than 10 million new active cases reported annually. In 2024 alone, the disease caused an estimated 1.2 million deaths, making it the leading cause of death from a single infectious agent.
“Administered together with first-line TB drug therapy, our intranasal DNA fusion vaccine helped infected mice clear the disease bacteria faster, reduced lung inflammation, and prevented relapse after treatment ended,” said Styliani Karanika, M.D., lead author of the study and faculty member at the Johns Hopkins Center for Tuberculosis Research.
The vaccine combines two genes—relMtb and Mip3α—to stimulate a targeted immune response. This fusion helps attract and activate dendritic cells, which play a crucial role in presenting TB-related proteins to T cells, thereby enabling a more effective immune attack on the bacteria.
Unlike traditional vaccines, the intranasal delivery method focuses the immune response directly in the lungs—the primary site of TB infection. This approach not only enhances localized immunity but also generates long-lasting systemic immune responses.
Preclinical studies demonstrated promising results. In mice, the vaccine improved bacterial clearance, reduced inflammation, and prevented relapse. Additionally, it enhanced the effectiveness of a powerful TB drug combination, suggesting potential benefits in treating drug-resistant TB cases.
Further testing in rhesus macaques showed that the vaccine generated durable immune responses in both the bloodstream and respiratory tract, lasting at least six months. While these findings are encouraging, researchers emphasized that additional studies are needed before progressing to human clinical trials.
“Our nonhuman primate data provide an important translational bridge between animal studies and future clinical applications,” added Karanika. “This approach could help shorten treatment durations and improve outcomes, particularly in difficult-to-treat TB cases.”
The study highlights a broader shift in TB treatment strategies, focusing on combining immunotherapy with antibiotics to target both active and persistent bacteria. Researchers note that DNA vaccines also offer practical advantages, including stability and efficient manufacturing, which could support large-scale deployment if proven effective in humans.
The research was supported by multiple funding sources, including grants from the National Institutes of Health, and represents a significant step forward in the global fight against tuberculosis.
