New Insights into How Tuberculosis Bacteria Evade Vaccines by Entering a Hiding State

Tuberculosis (TB) remains a significant global health challenge, with over 1.25 million fatalities annually. A vaccine has successfully protected more than 100 million infants each year from severe forms of TB, including life-threatening brain swelling. However, it does not prevent the development of TB in adults, especially the pulmonary form, which allows the disease to persist as the world's deadliest infectious killer.

Recent research from prominent institutions, including Tufts University, elucidates how TB bacteria manage to bypass the immune response even in vaccinated or previously infected hosts. The study, published in npj Vaccines, employed a technique called transposon insertion sequencing (TnSeq) to identify essential genes the bacteria rely on for survival under different immune conditions in mice.

The experimental design involved four groups of mice: one vaccinated with the traditional TB vaccine derived from bovine strains, another with an experimental human-based vaccine that elicited a stronger immune response, a third group that had recovered from TB following antibiotic treatment, and a control group with no prior exposure.

The findings revealed that, contrary to expectations, certain genes that are usually vital for TB growth and disease progression were less necessary once the bacteria encountered an immune response due to vaccination or past infection. Instead, the bacteria appeared to switch tactics by relying on different genetic pathways that help them endure stressful conditions and halt growth, effectively 'playing possum' to evade immune eradication. This dormant or slow-growing state allows TB bacteria to survive until the immune pressure wanes, such as through natural immune decline, HIV infection, or other immunocompromising conditions.

Furthermore, the study highlighted that different vaccines, or the methods of administration, could influence which bacterial genes are critical for persistence. This insight opens the possibility for developing more strategic vaccine combinations and treatments that target these survival mechanisms.

Dr. Amanda Martinot, a co-author of the study, emphasized the importance of this discovery, stating that comprehending how TB bacteria hide could lead to adjunct therapies that help immune systems clear latent bacteria more effectively. The researchers also noted that the genetic stability of Mycobacterium tuberculosis means that, in theory, a highly effective vaccine should be achievable, but the bacteria's ability to adapt complicates this goal.

This research underscores the urgent need for innovative approaches to TB prevention and treatment, particularly as resistant strains emerge. By understanding the bacterial 'play dead' strategy, scientists are now better equipped to design vaccines and therapies that prevent TB from hiding and reactivating, ultimately aiming to control and eradicate this persistent pathogen.

Source: medicalxpress.com