The study was led by Tel Aviv University’s Vice President for Research and Development Prof. Dan Peer, a global pioneer in mRNA drug development and director of the Laboratory of Precision NanoMedicine at the Shmunis School of Biomedicine and Cancer Research. He worked alongside researchers from the Israel Institute for Biological Research — Dr. Uri Elia, Dr. Yinon Levy, Dr. Emmy Mamroud, and Dr. Ofer Cohen — as well as members of his own laboratory team: Dr. Edo Kon, Dr. Inbal Hazan-Halevy, and doctoral student Shani Benarroch. The study was featured on the cover of the prestigious journal Advanced Science. 

The vaccine developed by the team from the Institute for Biological Research and Tel Aviv University is an mRNA-based vaccine delivered via lipid nanoparticles, similar to the COVID-19 vaccine. However, mRNA vaccines are typically effective against viruses like COVID-19 — not against bacteria like the plague.  

Dr. Uri Elia explains: “Viruses rely on a host cell to survive and replicate. They infect the cell with an RNA molecule (mRNA) that contains instructions for making viral proteins. The virus uses the cell as a factory to replicate itself. In an mRNA vaccine, this molecule is synthesized and encased in a lipid nanoparticle that resembles human cell membranes. The nanoparticle fuses with the cell, the cell produces the viral proteins, and the immune system learns to recognize and defend against the actual virus upon exposure. Bacteria, however, are a different story: they produce their own proteins and do not rely on human cells. Moreover, due to the different evolutionary paths of humans and bacteria, their proteins are very different from ours.” 

In 2023, the researchers developed a unique method for producing the bacterial protein within a human cell in a way that prompts the immune system to recognize it as a genuine bacterial protein and thus learn to defend against it. The researchers from Tel Aviv University and the Institute for Biological Research proved, for the first time, that it is possible to develop an effective mRNA vaccine against bacteria. They chose Yersinia pestis, the bacterium that causes bubonic plague — a disease responsible for deadly pandemics throughout human history. In animal models, the researchers demonstrated that it is possible to effectively vaccinate against the disease with a single dose. 

Prof. Dan Peer: “In the previous study, we developed a vaccine for a form of plague transmitted through the skin — for example, via flea bites. In the current study, we chose a much more ambitious target: pneumonic plague, which spreads from person to person and causes respiratory illness — making it particularly difficult to develop a vaccine against. For this reason, we used two proteins — two antigens — to create the vaccine. We tested it on several animal model strains and found that, after two vaccine doses, we achieved 100% protection against pneumonic plague: the animals infected with the plague did not get sick at all. The success of the current study paves the way for a whole world of mRNA-based vaccines against other deadly bacteria.” 

“The plague — a disease that killed about two-thirds of Europe’s population in the Middle Ages (‘The Black Death’) still resurfaces occasionally today, for example in Madagascar. So the potential for a pandemic still exists,” says Dr Uri Elia. “The disease is caused by a bacterium called Yersinia pestis, for which there is no approved vaccine in Western countries. This bacterium is highly contagious and extremely lethal, making it a serious threat. Moreover, this bacterium concerns us as a potential agent of bioterrorism. If one of our enemies tries to use it against us, we want to be prepared with a vaccine.”