World’s first mRNA vaccine against deadly plague bacteria is 100% effective
Researchers from Tel Aviv University and the Israel Institute for Biological Research developed the world's first messenger mRNA-based single-dose vaccine that is 100 percent effective against a lethal bacteria.
Published in the peer-reviewed journal Science Advances, the study suggests that this paves the way for developing more vaccines for bacterial diseases, including diseases caused by antibiotic-resistant bacteria. The study, conducted on mice, demonstrated that all vaccinated animals were fully protected against the bacteria that causes the plague.
Caused by the bacterium Yersinia pestis, plague is not a thing of the past. Every year, cases are reported in Africa, some parts of Asia, South America, and the U.S. Known for killing millions in the Middle Ages, people get infected with the plague after coming into contact with a rodent flea or being bitten by one infected with the plague.
Most mRNA vaccines being developed today are for viral infections, with pharmaceutical companies from all over the world rushing to address the need for a vaccine to prevent the spread of COVID-19. Not much work has been done on addressing mRNA-based vaccination against bacteria.
"So far, mRNA vaccines, such as the COVID-19 vaccines, which are familiar to all of us, were assumed to be effective against viruses but not against bacteria," explains Dr. Edo Kon, the study's lead author.
Most vaccines out there have a dead or weakened version of a bacteria or virus in them. The mRNA technology doesn't use actual bacteria or viruses.
The researchers explain that viruses produce their proteins inside our cells, meaning they depend on human cells for their reproduction.
Bacteria are a whole different story
Bacteria don't need human cells to produce proteins. Therefore, the proteins produced in bacteria can be different from those produced in human cells, even when based on the same genetic sequence.
"To address this problem, we developed methods to secrete the bacterial proteins while bypassing the classical secretion pathways, which are problematic for this application," explained Dr. Kon. "The result was a significant immune response, with the immune system identifying the proteins in the vaccine as immunogenic bacterial proteins. To enhance the bacterial protein's stability and make sure that it does not disintegrate too quickly inside the body, we buttressed it with a section of human protein. By combining the two breakthrough strategies, we obtained a full immune response."
Due to the excessive use of antibiotics over the last few decades, many bacteria have developed resistance to antibiotics, reducing the effectiveness of these important drugs, explains Professor Dan Peer, VP for R&D and head of the Laboratory of Precision Nano-Medicine at the Shmunis School of Biomedicine and Cancer Research at TAU.
The researchers believe that their study will be helpful in the development of safe and effective mRNA vaccines.
Messenger RNA (mRNA) lipid nanoparticle (LNP) vaccines have emerged as an effective vaccination strategy. Although currently applied toward viral pathogens, data concerning the platform's effectiveness against bacterial pathogens are limited. Here, we developed an effective mRNA-LNP vaccine against a lethal bacterial pathogen by optimizing mRNA payload guanine and cytosine content and antigen design. We designed a nucleoside-modified mRNA-LNP vaccine based on the bacterial F1 capsule antigen, a major protective component of Yersinia pestis, the etiological agent of plague. Plague is a rapidly deteriorating contagious disease that has killed millions of people during the history of humankind. Now, the disease is treated effectively with antibiotics; however, in the case of a multiple-antibiotic-resistant strain outbreak, alternative countermeasures are required. Our mRNA-LNP vaccine elicited humoral and cellular immunological responses in C57BL/6 mice and conferred rapid, full protection against lethal Y. pestis infection after a single dose. These data open avenues for urgently needed effective antibacterial vaccines.
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