Key points:
- For the first time, researchers have developed an mRNA vaccine for deadly bacteria.
- It was 100% effective when testing in animal models.
- The researchers say the technology is critical for future pandemics.
For the first time, a team of researchers from Tel Aviv University and the Israel Institute for Biological Research have developed an mRNA-based vaccine that is 100% effective against a type of bacteria that is lethal to humans. The study, conducted in an animal model, demonstrated that all treated animals were fully protected against the bacteria.
According to the researchers, their new technology can enable rapid development of effective vaccines for bacterial diseases, including diseases caused by antibiotic-resistant bacteria.
"Until now, scientists believed that mRNA vaccines against bacteria were biologically undoable. In our study we proved that it is in fact possible to develop 100%-effective mRNA vaccines for deadly bacteria,” said lead researcher Edo Kon.
Viruses depend on external cells for their reproduction. Inserting its own mRNA molecule into a human cell, a virus uses those cells as a factory for producing viral proteins based on its own genetic material, replicating itself. In mRNA vaccines this same molecule is synthesized in a lab, then wrapped in lipid nanoparticles resembling the membrane of human cells. When the vaccine is injected into the human body, the lipids stick to human cells, and consequently the cells produce viral proteins. The immune system, becoming familiar with these proteins, learns how to protect the body in the event of exposure to the real virus.
Bacteria, however, are a whole different story. They don't need human cells to produce their own proteins. Additionally, since the evolutions of humans and bacteria are quite different, proteins produced in bacteria can be different from those produced in human cells—even when based on the same genetic sequence.
Researchers have tried to synthesize bacterial proteins in human cells, but exposure to these proteins resulted in low antibodies and a general lack of protective immune effect. This is because, even though the proteins produced in the bacteria are essentially identical to those synthesized in the lab, being based on the same “manufacturing instructions,” those produced in human cells undergo significant changes, like the addition of sugars, when secreted from the human cell.
To address this problem, the research team developed methods to secrete the bacterial proteins while bypassing the classical secretion pathways, which are problematic for this application. The result, according to the paper published in Science Advances, was a significant immune response, with the immune system identifying the proteins in the vaccine as immunogenic bacterial proteins.
“To enhance the bacterial protein's stability and make sure that it does not disintegrate too quickly inside the body, we buttressed it with a section of human protein. By combining the two breakthrough strategies we obtained a full immune response,” said Kon.
When tested in mice, all unvaccinated mice died within a week of being infected with a deadly bacterium; whereas, all vaccinated mice remained alive and healthy. Additionally, the vaccination method comprised only one dose—something the researchers say is “crucial for protection against future outbreaks of fast-spreading bacterial pandemics.”
“If tomorrow we face some kind of bacterial pandemic, our study will provide a pathway for quickly developing safe and effective mRNA vaccines,” said Dan Peer, VP for R&D and Head of the Laboratory of Precision Nano-Medicine at Tel Aviv University.
Information provided by Tel Aviv University.