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A novel tuberculosis (TB) vaccine candidate developed at Texas Biomedical Research Institute has demonstrated superior protection compared to the widely used Bacille Calmette-Guerin (BCG) vaccine, according to a new preclinical study published in Nature Communications.
A Promising Breakthrough in TB Prevention
A team led by Professor Deepak Kaushal, Ph.D., has been working on an improved TB vaccine for over 15 years. Their latest research highlights the efficacy of a live-attenuated vaccine candidate, named delta sigH, which involves a modified strain of Mycobacterium tuberculosis (Mtb). The vaccine was shown to provide complete protection in rhesus macaques in earlier studies, and now, further testing in cynomolgus macaques has reinforced its potential for human application.
“Immunology has changed a lot in 10 years, and now we can do much more in-depth experiments that show not just that this vaccine works, but why it is working,” Dr. Kaushal said. “This study reveals the mechanisms behind its elite protection, which could help advance next-generation TB vaccines.”
The Urgent Need for a New TB Vaccine
TB remains the deadliest infectious disease globally, with over 1.25 million deaths and 10.6 million infections reported in 2023, according to the World Health Organization. The current BCG vaccine, developed more than a century ago, has limited effectiveness, particularly in adults, underscoring the need for an improved alternative.
Delta sigH offers a promising solution by deleting the gene responsible for producing the sigmaH (sigH) protein, which is crucial for the bacterium’s ability to survive oxidative stress in the lungs. This genetic modification weakens the pathogen, enabling the immune system to mount a stronger defense.
Enhanced Immune Response
Researchers employed advanced imaging techniques and single-cell RNA sequencing to analyze immune responses in animals vaccinated with either delta sigH or BCG. While both groups exhibited TB control, the delta sigH vaccine induced a more robust and balanced immune response.
Key findings include:
- Greater recruitment of critical B and T immune cells to the airways without excessive inflammation.
- Lower levels of IDO, a protein that exacerbates inflammation and hampers TB immunity.
- A shift in interferon response, favoring interferon gamma (Type II interferon), which enhances the immune system’s ability to combat TB more effectively than the Type I interferon response induced by BCG.
“With delta sigH, it looks like we are getting all of the good aspects of interferon signaling and none of the bad,” Dr. Kaushal explained.
The Road Ahead
Despite the promising results, several questions remain unanswered. Researchers are investigating the duration of protection, optimal delivery methods (whether via injection or direct lung administration), and the potential for multi-gene knockout versions of the vaccine for human trials.
“The next round of studies is already underway,” Dr. Kaushal confirmed. “While we are still years away from clinical application, these findings provide crucial insights into combating this persistent disease.”
Disclaimer
This article is based on preclinical research findings and does not constitute medical advice. Further studies and clinical trials are required to validate the safety and efficacy of the delta sigH vaccine in humans.
