In a groundbreaking advancement, researchers from the University of Pittsburgh, in collaboration with Cornell University, have engineered a self-destructing intravenous (i.v.) Bacillus Calmette-Guérin (BCG) vaccine. This innovative vaccine has shown promising results in preclinical trials,offering enhanced safety and protection against tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) in macaque monkeys.
The newly developed vaccine incorporates a built-in safety mechanism—a BCG “kill switch”—within the live, attenuated Mycobacterium bovis strain. This feature eliminates the risk of accidental self-infection with the weakened mycobacteria, providing a safer and more effective method to combat TB.As JoAnne Flynn, PhD, senior author of the study published in Nature Microbiology, explained, “Using a self-killing BCG strain may increase the safety of i.v. BCG vaccination strategies while maintaining remarkable protective efficacy.”
according to a 2024 World Health Institution report, TB remains the world’s deadliest infectious disease. Despite its global impact, effective and universally safe vaccination strategies have been elusive. The BCG vaccine, named after its developers, contains inactivated mycobacteria that infect cattle and is currently the only TB vaccine available for humans. Though, its effectiveness is limited. While it offers partial protection for young children when injected into the skin, it provides no protection for adults.
“BCG has probably been administered to more humans than any other vaccine and is generally safe,” the research team noted. “BCG protects children against disseminated TB and TB meningitis but is only partially protective against pulmonary TB.” They also highlighted that complications from BCG vaccination, though rare, can be fatal for immunocompromised children.
To address these limitations, Flynn and her team partnered with Cornell University to develop a more universally effective vaccine. Their work builds on Flynn’s earlier research, which demonstrated a 100,000-fold reduction in bacterial burden in the lungs of non-human primates (NHPs) when the BCG vaccine was administered intravenously, compared to the standard intradermal method. In that study, nine out of ten animals showed no signs of lung inflammation. “Typically, BCG is delivered by intradermal injection, but studies in non-human primates revealed that high-dose intravenous administration or endobronchial instillation result in excellent protection against M. tuberculosis,” the team explained.
The new self-destructing BCG vaccine represents a significant leap forward in TB prevention. By combining enhanced safety features with improved efficacy, this innovation could pave the way for more effective global TB control strategies. As the fight against tuberculosis continues, such advancements offer hope for a future where this devastating disease can be effectively managed and ultimately eradicated.
Revolutionizing TB Vaccination: The Breakthrough of the Kill-switch BCG Vaccine
In a groundbreaking development, researchers have unveiled a new version of the BCG vaccine, designed with a built-in “kill switch” to enhance safety and efficacy. This innovation could transform the fight against tuberculosis (TB), particularly for immunocompromised individuals.
conventional BCG vaccines, while effective, carry risks, especially for those with weakened immune systems.The new “kill-switch” BCG vaccine addresses these concerns by self-destructing after triggering the immune response, eliminating the possibility of vaccine-derived infections. In mouse trials,the modified vaccine provided protection comparable to the standard BCG vaccine but with faster clearance from the body,even in immunocompromised subjects. As the researchers noted, “Modified BCG elicited similar immune responses and provided similar protection against Mtb challenge as wild-type BCG in mice.”
The results were even more promising in macaque monkeys. monkeys vaccinated with the kill-switch BCG showed no detectable lung inflammation eight weeks after being exposed to live Mycobacterium tuberculosis. Remarkably, six out of eight monkeys had no recoverable traces of the bacteria, compared to just two out of eight in the standard BCG group.The researchers emphasized, “Our data indicate that this ‘kill-switch’ BCG strain induces greater CD4 T-cell responses in lungs and may provide even more robust protection than WT BCG in macaques.”
Dr. flynn, a key researcher on the project, highlighted the vaccine’s potential: “The live-attenuated form of the mycobacteria does not need to be alive for very long to provide outstanding protection and with this strain, there is essentially no chance for a vaccine-derived infection, even in an immunocompromised host.”
While the road to human trials presents challenges,the team remains optimistic. “We hope that this ‘kill switch’ BCG strain 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,” Flynn added.
this innovation not only promises to improve TB vaccination outcomes but also opens the door to safer immunization strategies for vulnerable populations. As research progresses, the kill-switch BCG vaccine could become a cornerstone in global efforts to eradicate tuberculosis.
