Researchers from Tel Aviv University and the Israel Institute for Biological Research have developed the world’s first mRNA vaccine effective against bacteria, scientists told the Times of Israel on Monday.
By modifying proven mRNA technology used to fight COVID and other viral pathogens, the scientists developed a single-dose vaccine that fully protects mice against the Plague, the lethal disease that killed millions of people during the Middle Ages and is still around today, especially in parts of Africa and Asia.
The researchers hope to adapt the vaccine for other diseases, especially ones caused by antibiotic-resistant bacteria that could lead to a fast-spreading pandemic.
“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,” said 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 at TAU.
“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,” he said.
Although the researchers are pleased with the results of their peer-reviewed study of the Plague-causing Yersinia pestis, published last week in Science Advances, they believe that other microbes are now the priority.
“The next step is to focus on bacteria that are more relevant for the general public now like Staphylococcus aureus and certain kinds of resistant Streptococcus,” said Dr. Edo Kon, the study’s lead author.
The advantage of mRNA vaccines is that they are now familiar, effective, and can be quickly developed. In the case of SARS-CoV2 (COVID-19), it took only 63 days to move from the publishing of the virus’s genetic sequence to clinical trials of the vaccine. Both the Moderna and Pfizer vaccines were mRNA vaccines.
The challenge with developing mRNA vaccines against bacteria derives from the fact that bacteria differ from viruses in a key way. Viruses depend on external (host) cells for their reproduction. They insert their mRNA molecule into human cells and use them as factories for producing viral proteins based on their genetic material.
In mRNA vaccines, the 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 the cells, leading the cells to produce viral proteins. The human immune system becomes familiar with these proteins and learns to protect the body in the event of exposure to the real virus.
“In contrast, bacteria 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.
As a result, attempts by scientists to synthesize bacterial proteins in human cells resulted in low levels of antibodies that produced an insufficient immune response.
To overcome this problem, the TAU and IIBR team developed methods to secrete the bacterial proteins while bypassing the classical secretion pathways. As a result, the immune system identified the proteins in the vaccine as immunogenic bacterial proteins. The bacterial protein was enhanced with a section of human protein to ensure its stability and guard against its disintegration too quickly inside the body.
“By combining the two breakthrough strategies we obtained a full immune response,” Kon said.
It worked for the Plague bacteria, and the next step will be to check whether this mechanism will work for other types of bacteria. According to Kon, the work is already underway.
“I have to stay true to science and say that we don’t know anything for sure about this yet, but at least now we have these important tools for further investigation,” he said.