Researchers from Tel Aviv University and the Institute for Biological Research have developed an innovative vaccine against one of the deadliest bacteria in history – Yersinia pestis, which caused the Black Death in the Middle Ages.
In a groundbreaking study, researchers from Tel Aviv University and the Ness Ziona Biological Institute used the coronavirus vaccine platform to produce the world's first mRNA-based vaccine against a deadly antibiotic-resistant bacterium. The researchers tested the vaccine's resistance to the virulent pathogen that causes the deadly disease, and were able to show 100% protection against infection in model animals. The researchers now hope that the technology demonstrated in this study can also be used against other deadly bacteria.
The research was conducted under the leadership of Tel Aviv University Vice President for Research and Development Prof. Dan Parr, one of the world's pioneers in mRNA drug development and head of the Nanomedicine Laboratory. Shemunis School of Biomedical Research and Cancer Research in the George S. Wise Faculty of Life SciencesAlongside him were the team of researchers from the Biological Institute: Dr. Uri Eliya, Dr. Yinon Levy, Dr. Ami Mamrod and Dr. Ofer Cohen from the Institute for Biological Research, as well as Prof. Parr's laboratory team: Dr. Ido Kun, Dr. Inbal Hazan-Halevi and doctoral student Shani Ben-Harush. The study was published on the cover of the prestigious journal Advanced Science.
The first mRNA vaccine against deadly bacteria
The vaccine developed by the team of researchers from the Biological Institute and Tel Aviv University is an mRNA-based vaccine carried by lipid nanoparticles, similar to the coronavirus vaccine. However, mRNA vaccines are effective against viruses like the coronavirus, not against deadly bacteria like this one.
Dr. Uri Eliya explains: "Viruses, or viruses, depend on an external cell ("host") to live and reproduce. They infect the cell with an RNA molecule (mRNA), which contains production instructions for the virus's proteins. Thus, the virus uses the cell as a factory to produce copies of itself. In an mRNA vaccine, this molecule is synthesized and wrapped in a fatty nano-envelope that resembles the cell membrane in the human body. Thus, the envelope penetrates the cell, the cell produces the virus's proteins, and the immune system learns to recognize it and defend itself against it in the event of exposure to the actual virus. Bacteria are a different story: the bacteria produces the proteins for itself, it doesn't need us for that. And because of the different evolution of humans and bacteria, its proteins are not at all similar to our proteins."
In 2023, researchers developed a special method for producing the bacterial protein in a human cell, in such a way that the immune system recognizes it as a real bacterial protein, and thus learns to protect itself against it. The research team demonstrated, for the first time, that it is possible to develop an effective mRNA vaccine against bacteria, and chose the bacterium Yersinia pestis, which causes bubonic plague, a disease that has caused deadly epidemics throughout human history. In model animals, the researchers demonstrated that it is possible to effectively vaccinate against the disease after a single dose of vaccine.
First step towards a global vaccine against the respiratory thing
"In the previous study, we developed a vaccine for a form of the disease in which the infection is transmitted through the skin, for example through a flea bite. In the current study, we chose a much more ambitious target: a respiratory virus, which, as its name suggests, is contagious from person to person and causes a respiratory disease - and therefore it is also very difficult to create a vaccine against it," explains Prof. Parr and continues, "For this reason, this time we used two proteins, two antigens, to create the vaccine. We tested our vaccine on model animals from several species, and we found that after two doses of vaccine we achieve 100% protection against the respiratory virus: the animals that were infected with the virus did not get sick at all. The success in the current study now also opens the door for us to the world of mRNA-based vaccines against other deadly bacteria."
"The bubonic plague killed about two-thirds of the population of Europe in the Middle Ages ("the Black Death"), and still breaks out from time to time today, for example in Madagascar, so the potential for a plague still exists," says Dr. Uri Eliya, concluding, "The causative agent of the disease is a bacterium called Yersinia pestis, against which there is no approved vaccine in Western countries. This bacterium is very contagious and very deadly, and therefore it is a serious threat. Moreover, this bacterium is also of interest to us as a potential bacterium that is on the list of bacteria for biological terrorism. If one of our enemies tries to use it against us, we want to be prepared with a vaccine."
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