Ep. 134 “Outsmarting Tuberculosis” Featuring Dr. Shabaana Khader
Tuberculosis remains the world's deadliest infectious disease, killing over 2.5 million people annually and infecting 10 million new cases each year—yet we still rely on a century-old vaccine. In this episode, Dr. Shabana Khader of the University of Chicago reveals how her lab is rethinking TB defense by focusing on the lung's immune environment, not just systemic responses. She argues that the key to a next-generation vaccine lies in training the immune system at the mucosal barrier—where TB first enters—using adjuvants that boost protective Th17 and lymphocyte-rich granulomas, rather than relying on outdated Th1-focused strategies. Her research shows that not all granulomas are equal: protective ones are lymphocyte-dominant, while disease-driving ones are fueled by inflammatory myeloid cells. This insight could revolutionize vaccine design by shifting from systemic delivery to lung-targeted immunization. Beyond science, Khader shares a powerful personal mantra: 'Be authentic'—a reminder that integrity in both research and life is the ultimate superpower in a world of constant change.
TB kills 2.5 million people yearly and infects 10 million new cases annually—making it the top infectious disease killer globally.
The BCG vaccine, used for over 100 years, only protects children and wanes after 10 years, leaving adolescents and young adults vulnerable.
Latent TB infects 2 billion people worldwide, with a 10% lifetime risk of progressing to active, transmissible disease.
Protective granulomas are lymphocyte-rich and contain the infection; disease-driving granulomas are myeloid-dominated and cause tissue damage.
Next-gen TB vaccines must be delivered to the lung mucosa to generate early Th17 responses and prevent bacterial establishment.
…and 3 more takeaways available in PodZeus
The Global Burden of Tuberculosis
“In the 30 minutes or so that we will be talking, another 30 to 50 people will die from TB.”
The Limits of BCG and the Need for a Booster
Despite being over a century old, BCG is still used globally due to its safety and non-specific protection. However, it wanes after 10 years, leaving young adults vulnerable. The episode explores why countries with low TB incidence avoid BCG due to interference with diagnostic tests.
Why Antibiotics Alone Can't Eradicate TB
The episode examines why short-term antibiotic regimens fail: TB hides in macrophages as persistent bacteria, and reinfection is common in high-incidence areas. The prolonged treatment is necessary to eliminate these reservoirs.
The Dual Nature of Granulomas: Protection vs. Pathology
“During protection the flavor of the granulomas are predominantly a lymphocyte flavored nature of the granulomas. And when you move towards TB disease, the disease and the inflammation that causes the disease is driven mostly by myeloid cells.”
Designing the Next-Generation TB Vaccine
“We must stop TB where it starts, which is in the lungs.”
“In the 30 minutes or so that we will be talking, another 30 to 50 people will die from TB.”
“during protection the flavor of the granulomas are predominantly a lymphocyte flavored. nature of the granulomas. And when you move towards TB disease, the disease and the inflammation that causes the disease is driven mostly by myeloid cells such as macrophages or neutrophils.”
“And my lab has really advocated for the thinking that we must stop TB where it starts, which is in the lungs.”
Hosts
Guest
tuberculosis
other
Dr. Shabana Khader
person
BCG vaccine
other
immunology podcast
media
planarians
other
TNF-alpha
other
University of Chicago
organization
activin
other
HIV-1
other
acute pancreatitis
other
Start discovering podcast insights today
Start with a 7-day trial and explore a growing catalog of popular podcasts. No credit card required.
No credit card required • 7-day trial • Cancel anytime