Scientists from Tel Aviv University and the Israel Institute for Biological Research have developed the world’s first mRNA vaccine effective against bacteria, researchers told the Times of Israel on Monday.
By modifying proven mRNA technology used to fight COVID and other viral pathogens, scientists have developed a one-time vaccine that fully protects mice from the plague, a deadly disease that killed millions in the Middle Ages and is still prevalent today, especially in parts of Africa and Asia.
The researchers hope to adapt the vaccine to other diseases, especially those caused by antibiotic-resistant bacteria that could lead to a fast-spreading pandemic.
“There are many pathogenic bacteria for which we do not have vaccines. In addition, due to the overuse of antibiotics in the last few decades, many bacteria have developed resistance to antibiotics, reducing the effectiveness of these important drugs,” said Prof. Dan Peer, vice president for research and development and head of the Laboratory of Precision Nano-Medicine at the Shmunis School of Biomedicine and Cancer Research at TAU.
“As a result, antibiotic-resistant bacteria are already a real threat to human health worldwide. The development of 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 study of plague-causing Yersinia pestis, published last week in Science Advances, they believe other microbes are now the priority.
“The next step is to focus on bacteria that are now more relevant to the general public, such as Staphylococcus aureus and certain types of resistant streptococci,” said Dr. Edo Kon, lead author of the study.
The advantage of mRNA vaccines is that they are now known, effective and can be developed quickly. In the case of SARS-CoV2 (COVID-19), it took only 63 days from the publication of the genetic sequence of the virus to clinical trials of the vaccine. Both the Moderna and Pfizer vaccines were mRNA vaccines.
The problem with developing mRNA vaccines against bacteria stems from the fact that bacteria differ from viruses in a key way. Viral reproduction depends on external (host) cells. They insert their mRNA molecule into human cells and use them as factories to produce viral proteins based on their genetic material.
In mRNA vaccines, the molecule is synthesized in the laboratory and then packaged 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 to the production of viral proteins. The human immune system becomes familiar with these proteins and learns to protect the body when exposed to the real virus.
“In contrast, bacteria do not need our cells to produce their own proteins. And because the evolution of humans and bacteria is quite different from each other, proteins produced in bacteria can be different from proteins produced in human cells, even if they are 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 elicited an inadequate immune response.
To overcome this problem, the TAU and IIBR team developed methods to secrete bacterial proteins while bypassing classical secretion pathways. As a result, the immune system identified the proteins in the vaccine as immunogenic bacterial proteins. The bacterial protein has been enhanced with a portion of human protein to ensure its stability and protection from breaking down too quickly inside the body.
“By combining two breakthrough strategies, we obtained a full immune response,” Kon said.
It worked in Plague bacteria, and the next step will be to check if this mechanism works in other types of bacteria. According to Kon, work is already underway.
“I have to stay true to the 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.