Researchers from Tel Aviv University (TAU) and the Israel Institute for Biological Research in Ness Ziona have used the platform developed for COVID-19 vaccines to create the world’s first mRNA-based vaccine against a deadly, antibiotic-resistant bacterium.

In the groundbreaking study, the researchers tested the vaccine’s resistance to the virulent pathogen that causes the disease and were able to demonstrate 100% protection against infection in animal models. The researchers now hope that this technology can be used to combat other lethal bacteria as well.

The study was led by Professor Dan Peer, TAU’s Vice President for Research and Development, a global pioneer in mRNA drug development and director of the Laboratory of Precision NanoMedicine at TAU’s Shmunis School of Biomedicine and Cancer Research. He worked alongside researchers from the Israel Institute for Biological Research 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 April 25, 2025, issue of Advanced Science.

The vaccine 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.

“Viruses rely on a host cell to survive and replicate,” Dr. Uri Elia of the Israel Institute for Biological Research explains. “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 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.

“In the previous study, we developed a vaccine for a form of plague transmitted through the skin — for example, via flea bites,” Professor Peer says. “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,” Dr. Elia concludes. “The disease is caused by 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.”