World's First mRNA Vaccine for Antibiotic-Resistant Bacteria

For the first time, a team of Tel Aviv University and Israel Institute for Biological Research researchers created an mRNA-based vaccine that is 100% effective against a form of bacterium that is harmful to humans. The study, which was carried out in an animal model, revealed that all treated animals were completely protected against germs. According to the researchers, this new technology will allow for the rapid production of effective vaccinations for bacterial infections, particularly those caused by antibiotic-resistant bacteria, in the event of a new pandemic. Dr. Edo Kon of Tel Aviv University and Prof. Dan Peer, VP for R&D and Head of the Laboratory of Precision Nano-Medicine at the Shmunis School of Biomedicine and Cancer Research, led the study in collaboration with Dr. Yinon Levy, Uri Elia, Dr. Emanuelle Mamroud, and Dr. Ofer Cohen of the Israel Institute for Biological Research. The findings of the study were reported in the journal Science Advances.

mRNA Vaccine is Effective Against Bacteria

Edo Kon explains, "So far mRNA vaccines, such as the COVID-19 vaccines familiar to all of us, were assumed to be effective against viruses but not against bacteria. The great advantage of these vaccines, in addition to their effectiveness, is the ability to develop them very quickly: once the genetic sequence of the virus SARS-CoV2 (COVID-19) was published, it took only 63 days to begin the first clinical trial. However, until now scientists believed that mRNA vaccines against bacteria were biologically undoable. In our study, we proved that it is possible to develop 100%-effective mRNA vaccines for deadly bacteria."

The researchers explain that viruses require external (host) cells to reproduce. A virus exploits our cells as a factory for generating viral proteins based on its genetic material, essentially replicating itself, by inserting its mRNA molecule into a human cell. This same molecule is generated in a lab and then encased in lipid nanoparticles that mimic the membrane of human cells in mRNA vaccines. As we inject the vaccine into our bodies, the lipids adhere to our cells, causing the cells to create viral proteins. When the immune system becomes acquainted with these proteins, it learns how to protect our bodies in the event of an actual virus encounter.

Immune Response in mRNA Vaccine

Kon adds, "Since viruses produce their proteins inside our cells, the proteins translated from the viral genetic sequence are similar to those translated from the lab-synthesized mRNA. Bacteria, however, are a whole different story: They don't need our cells to produce their proteins. And since the evolutions of humans and bacteria are quite different from one another, 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, in our bodies. 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, we developed methods to secrete the bacterial proteins while bypassing the classical secretion pathways, which are problematic for this application. The result 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."

Prof. Peer said, "There are many pathogenic bacteria for which we have no vaccines. Moreover, due to the excessive use of antibiotics over the last few decades, many bacteria have developed resistance to antibiotics, reducing the effectiveness of these important drugs. Consequently, antibiotic-resistant bacteria already pose a real threat to human health worldwide. Developing a new type of vaccine may provide an answer to this global problem. In our study, we tested our novel mRNA vaccine in animals infected with a deadly bacterium. Within a week, all unvaccinated animals died, while those vaccinated with our vaccine remained alive and well. Moreover, in one of our vaccination methods, one dose provided full protection just two weeks after it was administered. The ability to provide full protection with just one dose is crucial for protection against future outbreaks of fast-spreading bacterial pandemics. It is important to note that the COVID-19 vaccine was developed so quickly because it relied on years of research on mRNA vaccines for similar viruses. If tomorrow we face some kind of bacterial pandemic, our study will provide a pathway for quickly developing safe and effective mRNA vaccines."

Source-Medindia