While there is evidence that messenger RNA (mRNA) vaccines are effective against viral infections, there is less information about the efficacy of this platform against bacterial pathogens. New research, "A single-dose F1-based mRNA-LNP vaccine provides protection against the lethal plague bacterium," was published in the peer-reviewed international journal Science Advances. Researchers at Tel Aviv University and other Israeli institutions claimed to have created the first mRNA vaccine with the potential to be 100% effective against a bacterium that is lethal to humans.
Researchers observed that with this unique strategy, all treated animals were protected against infection by the bacteria (Yersinia pestis) in animal models, suggesting that this approach might speed up the development of effective vaccines against bacterial infections, particularly those caused by antibiotic-resistant bacteria.
So far, mRNA vaccines (such as the mRNA vaccine against COVID-19) have been shown to be effective against viral infections but not bacterial infections. However, the biggest advantage of such vaccines, in addition to their effectiveness, is that they can be developed very quickly, with researchers needing only 63 days to begin first clinical trials once the genetic sequence of a virus such as SARS-CoV-2 is published, explained researcher Edo Kon.
The scientists revealed that "viruses become dependent on host cells for reproduction by inserting their own mRNA molecules into human cells," and that "viruses are able to replicate themselves by using our cells as factories to produce viral proteins based on their own genetic material." This identical molecule can be synthesized in a lab and used in an mRNA vaccine, where it is encased in lipid nanoparticles that mimic human cell membranes. When injected into the body, the vaccine's lipids bind to cells, prompting them to create viral proteins. Once the immune system recognizes these proteins, it may mount an effective defense against future infections.
Proteins translated from viral genetic sequences are similar to those translated from mRNA synthesized in the lab because viruses use the host's cells to make their own proteins. However, bacteria may be an entirely different story because they can make their own proteins without the host's cells, and because humans and bacteria did not evolve in the same way, the proteins produced by bacteria are different from those produced by human cells, even when based on the same genetic sequence.
For this reason researchers have attempted to synthesize bacterial proteins in human cells, but exposure to these proteins results in low antibody levels and a general lack of protective immune responses. This may be because, although the proteins produced by bacteria are essentially the same as those synthesized in the laboratory and are based on the same "manufacturing instructions", the proteins produced in human cells undergo significant changes when they are secreted from human cells, such as increased levels of sugar molecules.
Researchers have found techniques to produce bacterial proteins while avoiding the standard secretion pathway as a solution to this issue. The most substantial immunological response occurs via this route, which arises when the immune system mistakes the protein in the vaccine for an immunogenic bacterial protein. Professor Peer explained that by combining two innovative approaches, they were able to elicit a complete immune response, and the bacterial protein was reinforced with a fragment of the human protein to make it more stable and less susceptible to rapid breakdown in the body. "There are numerous infectious microorganisms for which there is not a vaccine available. As a result of widespread antibiotic misuse in recent decades, many bacteria have become resistant to these antibiotics. Thus, antibiotic-resistant bacteria have become a global health crisis, and the creation of a revolutionary vaccine might pave the way to better care for people."
In this study, researchers tested the effectiveness of a novel mRNA vaccine in treating animals infected with lethal bacteria. All unvaccinated animals died within a week, while those vaccinated with the novel vaccine survived well. In addition, in one of the vaccine strategies, one dose of the vaccine provided full protection to the animal organism after two weeks of use. This is critical to ward off future epidemics and outbreaks of rapidly spreading bacteria.