1/10/2025
The in-built safety mechanisms circumvent the possibility of an accidental self-infection with weakened mycobacteria, offering a safe and effective way to combat the disease that was named as the deadliest of 2024 by the World Health Organization.
“Although the idea of intravenous vaccination with a live vaccine may sound scary, it was very effective in our previous studies in non-human primates. Here, we focused on the safety aspect of IV vaccination and used a strain of mycobacteria that kills itself once administered to the animals. To our surprise, it was equal or slightly better than the regular TB vaccine in protecting monkeys against infection, providing sterilizing immunity in almost all animals,” said JoAnne Flynn, Ph.D., distinguished professor and chair of microbiology and molecular genetics at Pitt. “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.”
To develop a more universally effective vaccination approach, Flynn partnered with colleagues at Cornell University. In Flynn’s earlier work in macaque monkeys with collaborators at the National Institutes of Health, researchers saw a 100,000-fold reduction in bacterial burden in the lungs of animals who were given the BCG vaccine intravenously compared with the standard intradermal route. Nine out of 10 animals showed no inflammation in their lungs.
Despite the additional challenges of clinical testing required for expanding the use of the updated BCG vaccine in humans, researchers are optimistic.
The other senior authors of this research are Dirk Schnappinger, Ph.D., and Sabine Ehrt, Ph.D. of Weill Cornell Medicine. Other authors of this research are Alexander Smith, Ph.D., Pauline Maiello, M.S., H. Jacob Borish, Ph.D., Caylin Winchell, Ph.D., Andrew Simonson, Ph.D., Philana Ling Lin, M.D., Mark Rodgers, M.S., Daniel Fillmore and Jennifer Sakal, all of Pitt; and Hongwei Su, Ph.D., Joshua Wallach, Yao Liu, Ph.D., Kan Lin, Ph.D., Valerie Vinette, Ph.D., all of Weill Cornell Medicine.
PHOTO DETAILS: click images for high-res versions
Left photo
CAPTION: JoAnne Flynn, Ph.D.
CREDIT: Mike Drazdzinski
Right photo
CAPTION: PET-CT scan images of monkey lungs. While unvaccinated macaque monkeys exhibited signs of severe lung inflammation and disease following the Mycobacterium tuberculosis infection (warm colors indicate inflammation and disease, bottom row), monkeys that received the intravenously administered Kill-Switch BCG vaccine (middle row) were equally or better protected against the infection as those immunized with the standard BCG vaccine (top row).
CREDIT: Pauline Maiello
