July 27, 2021
Focus of the work is bolstering B-cell immunity to help body beat bacteria
Scientists from the Hackensack Meridian Center for Discovery and Innovation (CDI) were awarded $6.4 million from the National Institutes of Health (NIH) to pursue an innovative new tuberculosis (TB) vaccine concept.
The only TB vaccine available, Bacille Calmette-Guérin, or BCG, is very unreliable. The team proposes to improve BCG by engineering it to stimulate the development and communication of B cells, an important part of the immune system. With this strategy, the researchers hope to develop a second-generation TB vaccine which provides reliable protection from new infections and can even help to cure existing TB infections by complementing antibiotic therapy.
The novel approach could prove to be a critical breakthrough in the infection, which kills 1.4 million annually, and mostly in the developing world.
“This strategy of designing a B cell targeting TB vaccine is completely new and has not been tried before,” said Martin Gengenbacher, an assistant member of the CDI, and leader of the project. “Right now, we have five novel recombinant BCG vaccine candidates that are ready to be tested in our advanced preclinical models. We are excited it could make a huge difference for global health.”
“This grant shows the promise of Gengenbacher’s work,” said David Perlin, PhD., the chief scientific officer and senior vice president of the CDI. “If it proves efficacious, this could be a game changer for this devastating disease which still kills 1.4 million people globally each year but flies under the radar all too often in the developed world.”
BCG, the existing vaccine, has been around for a century. But it has limitations, since it has proven only effective in children and doesn’t fully prevent disease. That leaves adults, who make the majority of clinical TB cases unprotected – accounting for a staggering 10 million new cases per year.
The BCG replacement vaccine VPM1002 was invented by Gengenbacher’s mentor Stefan Kaufmann, Ph.D., of the Max Planck Institute for Infection Biology, who gave a talk in December 2019 at the CDI. Gengenbacher completed genetic modifications before large clinical trials could be pursued. VPM1002 is heading toward full clinical development and production.
Gengenbacher and the team propose a different strategy than most other researchers: increase quantity and life span of the body’s own B cells to fight the TB bacteria. Using high parameter flow cytometry available at the CDI, Gengenbacher and his team have identified a novel type of B-cells that contribute to the control of TB infection. The translational approach involves CDI scientists genetically engineering BCG to promote B cell development and survival – which also presumably includes their newly discovered protective B cell subsets.
Consequently, the scientists hypothesize the body will effectively fight off the bacteria.
“Our researchers at Hackensack Meridian Health have done incredible work to advance care for our patients, as we showed during the COVID-19 pandemic,” said Ihor Sawczuk, M.D., FACS, chief research officer and Northern Region president for the network. “But we also have a global reach to improve the lives of patients, like with this promising TB project.”