The platform that was developed for COVID-19 vaccines and saved millions of lives has been used in a world first by Israeli researchers to create a new vaccine based on mRNA (messenger RNA) against a lethal bacterium.
A single-stranded molecule that carries genetic information from the DNA in a cell to the ribosomes where proteins are synthesized, mRNA acts as a template, dictating the instructions for building specific proteins within a cell.
The researchers from Tel Aviv University (TAU) and the Israel Institute for Biological Research in the city of Nes Ziona say that their groundbreaking study tested the vaccine’s resistance to the virulent pathogen that causes the disease and that they were able to provide 100% protection against infection in animal models. The researchers now hope this technology, traditionally used against viral antigens and cancer, can be used to combat other lethal bacteria as well and eventually help protect mankind.
The study was led by TAU’s vice president for research and development Prof. Dan Peer, who is a global pioneer in mRNA drug development and has been director of the Laboratory of Precision NanoMedicine at the university’s Shmunis School of Biomedicine and Cancer Research since 2020. He worked alongside researchers from the Nes Ziona facility – Dr. Uri Elia, Dr. Yinon Levy, Dr. Emmy Mamroud, and Dr. Ofer Cohen – as well as members of his own lab team: Dr. Edo Kon, Dr. Inbal Hazan-Halevy, and doctoral student Shani Benarroch.
It has just been featured on the cover of the prestigious journal Advanced Science – an interdisciplinary science journal publishing the best-in-class fundamental and applied research in materials science, physics, medical and life sciences, chemistry, and engineering – under the title “Novel Bivalent mRNA-LNP Vaccine for Highly Effective Protection against Pneumonic Plague.”
The team of men and women were highly protected against the deadly bacteria at the Nes Ziona facility and not put in danger.
BUBONIC PLAGUE is a bacterial infection in the lymph nodes, while pneumonic plague is such an infection in the lungs; the only difference is the location.
The vaccine is an mRNA-based one delivered via lipid nanoparticles, similar to the COVID-19 vaccine. However, while such vaccines are typically effective against viruses like COVID-19, they are not effective against deadly diseases such as bubonic plague caused by the Yersinia pestis bacteria, which led to the Black Death pandemic in Europe in the mid-14th century, transmitted via the bite of an infected rodent flea or by handling an infected animal. This bacterium has been responsible for horrific pandemics throughout human history.
Peer told The Jerusalem Post that his team didn’t observe any side effects. They worked on a mouse model and hope to work with higher animals in another two months or so, after which it can be implemented on people quite fast. “We could use it to kill off nosocomial bacteria that infect patients with weakened immune systems only because they’re hospitalized or in a geriatric hospital or residence,” he said. “It’s a matter of priorities.”
It is possible to develop an effective mRNA vaccine against bacteria
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 TAU and Nes Ziona researchers proved, for the first time, that it is possible to develop an effective mRNA vaccine against bacteria and that it’s possible to effectively vaccinate against the disease with a single dose.
Peer related that just last week, a patient diagnosed with pneumonic plague was reported to have died at Flagstaff Medical Center north of Phoenix, Arizona; he was apparently exposed to an infected prairie dog or other rodent that was bitten by a flea. The doctors said it developed very quickly and is very difficult to diagnose. In 2017, more than 500 people in Madagascar were infected and died. “Fortunately, we haven’t seen a case in Israel, even though there are prairie dogs here.”
TAU’s vice president for research and development said that they worked on the project for two-and-a-half years and were very satisfied with their discoveries. “We got excellent reactions, especially from the US military. Unfortunately, the US Secretary of Health, Robert Kennedy Jr., doesn’t like vaccines in general and tries to discourage their use.”
NES ZIONA fellow researcher Dr. Elia explained that “viruses rely on a host cell to survive and multiply. They infect the cell with mRNA that contains instructions for making viral proteins. The virus uses the cell as a factory to replicate itself.
“In an mRNA vaccine, the molecule is synthesized and encased in a lipid nanoparticle that resembles human cell membranes. Then the nanoparticle fuses with the cell, which produces the viral proteins, and the immune system learns to recognize and defend against the actual virus upon exposure,” Elia said.
“Bacteria, however, are a different story: they produce their own proteins and do not rely on human cells. Additionally, due to the different evolutionary paths of humans and bacteria, their proteins are very different from ours, so the potential for a pandemic still exists,” he said.
“In the previous study, we developed a vaccine for a form of plague transmitted through the skin – for example, via flea bites,” said Peer, who with his team has done innovative and groundbreaking work in cancer, mostly in brain, ovarian, and blood and inflammatory bowel diseases.
The professor has more than 140 pending and granted patents; some of them have been licensed to several pharmaceutical companies and one is currently under registration as a new drug in inflammatory bowel disease. In addition, based on his work, five spin-off companies were generated aiming to bring personalized medicine into clinical practice.
“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 it,” Peer said. “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 team said.
“The plague killed about two-thirds of Europe’s population in the Middle Ages and was responsible for three major pandemics. The bacterium is highly contagious and extremely lethal, making it a serious threat,” Peer said.
“Moreover, this bacterium concerns us as a potential agent of bio-terrorism despite modern medical advances,” he concluded. “If one of our enemies tries to use it against us, we want to be prepared with a vaccine.”