Researchers from Tel Aviv University and the Israel Institute for Biological Research have developed an mRNA-based vaccine found to be 100 percent effective against a deadly type of bacteria when tested in lab animals.

According to the researchers, their new technology can enable rapid development of effective vaccines for bacterial diseases, including diseases caused by antibiotic-resistant bacteria.

Led by Tel Aviv University’s Dr. Edo Kon and Prof. Dan Peer, VP for R&D and head of the Laboratory of Precision Nano-Medicine, the study was published in the journal Science Advances.

“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,” said Peer.

“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.”

Kon explained, “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 this study, scientists believed that mRNA vaccines against bacteria were biologically impossible.

“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 own 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,” Kon said.

“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 team 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,” Kon said.

Peer pointed out that the excessive use of antibiotics over the last few decades has led many bacteria to develop resistance to antibiotics, which poses a threat to human health worldwide.

“Developing a new type of vaccine may provide an answer to this global problem. 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.”

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