Israeli researchers develop mRNA vaccine that conferred rapid, full protection against lethal Y. pestis infection in mice after a single dose
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For the first time worldwide, a team of researchers from Tel Aviv University and the Israel Institute for Biological Research has developed an mRNA-based vaccine that is 100% effective against a type of bacteria deadly to humans. The study, which was conducted in a lab model, showed that all treated models were completely protected from the bacteria. The researchers believe their new technology could enable the rapid development of effective vaccines for bacterial diseases, including those caused by antibiotic-resistant bacteria, for example in the event of a rapidly spreading new pandemic.
The results of the study have been published in the journal Science advances.
“Until now, mRNA vaccines, like the COVID-19 vaccines we are all familiar with, were assumed to be effective against viruses but not against bacteria,” explains Dr. Ido Kon. “The big advantage of these vaccines, in addition to their effectiveness, is the ability to develop them very quickly: once the genetic sequence of the SARS-CoV2 (COVID-19) virus was published, it took just 63 days to start the first clinical trial. However, until now, scientists believe that vaccines mRNA against bacteria would not have been biologically achievable. In our study we demonstrated that it is, in fact, possible to develop mRNA vaccines that are 100% effective against deadly bacteria.”
“We have demonstrated in our study that it is, in fact, possible to develop mRNA vaccines that are 100 percent effective against deadly bacteria.” Dr. Ido Kun
The researchers show that viruses depend on external (host) cells for their reproduction. By inserting its mRNA molecule into a human cell, the virus uses our cells as a factory to produce viral proteins based on its genetic material, i.e., repeats of itself.
In mRNA vaccines, this same molecule is synthesized in the laboratory, then wrapped into lipid nanoparticles that resemble the membrane of human cells. When the vaccine is injected into the body, the fat sticks to our cells, so the cells produce viral proteins. The immune system recognizes these proteins, and learns how to protect our bodies in the event of exposure to the real virus.
Because viruses produce their own proteins inside our cells, the proteins translated from the viral genetic sequence are similar to those translated from mRNA synthesized in the laboratory.
“If tomorrow we face some kind of bacterial pandemic, our study will provide a path to rapidly developing safe and effective mRNA vaccines.” Professor Dan Beer
However, bacteria are a completely different story: they don’t need our cells to produce their own proteins. Since the evolutions of humans and bacteria are so different from each other, the proteins produced in bacteria can differ from those produced in human cells, even when they are based on the same genetic sequence.
“The researchers tried to synthesize bacterial proteins in human cells, but exposure to these proteins resulted in decreased antibodies and a general lack of a protective immune effect in our bodies,” explains Dr. Kuhn. “This is because, although the proteins produced in bacteria are essentially identical to those made in a laboratory, based on the same ‘manufacturing instructions’, those produced in human cells undergo significant changes, such as the addition of sugars, when they are secreted from human cell”.
To address this issue, we have developed methods to secrete bacterial proteins while bypassing traditional 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 stability of the bacterial protein and ensure that it does not degrade too quickly within the body, we fortified it with a human protein fraction. By combining the two breakthrough strategies, we got a complete immune response.”
Solving antibiotic-resistant bacteria?
“There are many pathogenic bacteria for which we do not have vaccines,” adds Professor Beer. Moreover, due to the excessive use of antibiotics over the past few decades, many bacteria have developed resistance to antibiotics, which reduces the effectiveness of these important medications. Thus, antibiotic-resistant bacteria are indeed 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 new mRNA vaccine on animals infected with a deadly bacteria. Within a week, all unvaccinated animals died, while animals vaccinated with our vaccine remained alive and well. Moreover, in one of our vaccination methods, a single dose provides Full protection after only two weeks of administration Being able to provide full protection with just one dose is critical to protecting against future outbreaks of rapidly spreading bacterial epidemics It is important to note that the COVID-19 vaccine was developed very quickly because it was based on years of vaccine research mRNA of similar viruses. If tomorrow we face some kind of bacterial pandemic, our study will provide a path to quickly develop safe and effective mRNA vaccines.”