Self-destructing Tuberculosis Vaccination Offers Enhanced Protection

Tuberculosis (TB), declared the deadliest disease of 2024 by the World Health Organization, continues to pose a significant global health challenge. The current vaccination offered against TB, Bacillus Calmette-Guérin (BCG), provides no protection against TB in adults and only partial protection in young children. Despite the public health burden associated with TB there remains a lack of effective and safe protection strategies.

A recent study published in Nature Microbiology, conducted at the University of Pittsburgh investigates a self-destructing vaccination as a more protective and safe approach. The traditional BCG vaccine, given intradermally, contains inactivated Mycobacterium bovis. The researchers wanted to assess a live TB vaccine given intravenously as in a previous study it was found that intravenous (IV) administration of the BCG vaccine resulted in a 100,000-fold reduction in the pulmonary bacterial burden in animals compared to those who received standard intradermal route.

To address the safety concerns with a live IV vaccine researches engineered two strains of BCG with built-in safety mechanisms. These ‘kill switch’ mechanisms ensure that the vaccine self-destructs either upon withdrawal of or exposure to antibiotic doxycycline. Experiments conducted on mice revealed the engineered BCG provided comparable protection against TB to the standard BCG. However the engineered BCG provided faster elimination and improved safety, even in immunocompromised mice.

The study also discovered that the engineered IV BCG resulted in a stronger immune response and better protection compared to the standard IV BCG in macaque monkeys. Eight weeks after administration, no detectable lung inflammation was observed in monkeys vaccinated with the engineered IV BCG. While in contrast to this, two of the eight monkeys receiving the standard IV BCG displayed significant inflammation.

Moreover, with the standard IV BCG six out of eight monkeys were found to have recoverable live Mycobacterium Tuberculosis compared with only two out of eight monkeys who received the engineered vaccine.

The data indicates that the engineered BCG “induces greater responses in the lungs and may provide even more robust protection than [standard] BCG in macaques” senior author Dirk Schanppinger explains.

Co-author Joanne Flynn adds that this engineered “kill switch” could “limit safety concerns over intravenous vaccine administration and provide an option for a safer and more effective vaccination route for individuals who are immunocompromised”.