Johns Hopkins Researchers Develop Nasal DNA Vaccine to Combat Tuberculosis

Tuberculosis (TB) remains the leading cause of death from a single infectious disease globally. Even as antibiotic treatments exist, the bacteria often employ a stubborn defense mechanism, creating “persisters” that survive therapy and lead to disease relapse. However, a research team from Johns Hopkins Medicine and the Johns Hopkins Bloomberg School of Public Health has developed a promising solution: a therapeutic intranasal DNA vaccine designed to eliminate these resilient bacteria.

Targeting the “Persisters”: The Challenge of TB Treatment

The primary obstacle in treating tuberculosis is the emergence of drug-tolerant bacterial persisters. These bacteria can survive prolonged courses of antibiotics, remaining dormant in the body only to cause a relapse after treatment ends. Because multidrug regimens are long and tough for patients to complete, these persisters—along with the rise of drug-resistant TB strains—pose a significant threat to global health.

According to the World Health Organization (WHO), approximately 2 billion people, or one-quarter of the global population, carry a latent, symptom-free TB infection. In 2024, the WHO reported that more than 10 million people developed active TB disease, resulting in 1.2 million deaths. To address this, the WHO has called for the development of therapeutic vaccines that can be used alongside standard drug therapies to shorten treatment times and improve patient outcomes.

How the Nasal DNA Fusion Vaccine Works

Published in the Journal of Clinical Investigation, the study details a vaccine that fuses two specific genes: relMtb and Mip3α. Unlike traditional vaccines that prevent initial infection, this is a therapeutic vaccine intended for those already infected.

The vaccine is delivered through the nose (intranasal delivery) to capture advantage of three beneficial biological activities. Its primary goal is to direct the immune system to identify and destroy the drug-tolerant bacterial survivors that typically endure antibiotic treatment.

Key Findings from the Study

Lead author Styliani Karanika, M.D., a faculty member of the Johns Hopkins Center for Tuberculosis Research, noted that the vaccine showed significant efficacy in preclinical trials. When administered to infected mice alongside first-line TB drug therapy, the intranasal DNA fusion vaccine achieved several critical results:

• Faster Clearance: Infected mice cleared the disease bacteria more quickly.
• Reduced Inflammation: The vaccine helped reduce lung inflammation.
• Relapse Prevention: The treatment prevented the disease from returning after the therapy ended.

Expanding Treatment for Drug-Resistant TB

Beyond first-line therapies, the researchers found that the vaccine enhanced the effectiveness of a powerful drug combination used to treat hard-to-treat cases: bedaquiline, pretomanid and linezolid. This suggests that the nasal DNA vaccine could be a vital tool in fighting drug-resistant TB, helping the body eliminate bacteria even when standard medications struggle to do so alone.

Frequently Asked Questions

What is a therapeutic vaccine?

Unlike a prophylactic vaccine, which prevents a person from contracting a disease, a therapeutic vaccine is administered to people who already have the disease to help their immune system fight the infection more effectively.

Why is a nasal delivery method used?

Intranasal delivery allows the vaccine to target the respiratory system directly, taking advantage of specific biological activities in the nasal passages to prime the immune response against TB bacteria in the lungs.

Is this vaccine available for humans?

The current findings are based on research involving infected mice. While the results are promising for meeting the WHO’s call for shorter TB treatment regimens, further research is required before human application.

Looking Ahead

The development of this intranasal DNA fusion vaccine marks a significant step toward overcoming the persistence of tuberculosis. By combining immunotherapy with existing antibiotic regimens, researchers hope to reduce the duration of treatment and eliminate the risk of relapse, potentially saving millions of lives worldwide.