. If not successfully treated, a UTI can lead to sepsis, which can be fatal.
Even if the infection is cleared from the bladder, populations persist elsewhere and usually become resistant to the antibiotic used. When patients accumulate antibiotic resistance, they’re eventually going to run out of options.
At the same time, researchers were creating whole-cell vaccines by preserving antigens in this slow-release depot but there were no real models to test it with, and so they thought UTI presented a very good opportunity.
Vaccines work by introducing a small amount of killed or weakened disease-causing germs, or some of their components, to the body. These antigens prompt the immune system to produce antibodies against a particular disease.
Building vaccines against pathogenic bacteria is inherently difficult because bacteria are significantly larger and more complex than viruses. Selecting which biological components to use to create antigens has been a major challenge.
Consequently, using the entire cell is preferable to choosing just a piece of a bacterium.
Vaccines using whole-cell dead bacteria haven’t succeeded because the cells typically don’t last long enough in the body to produce long-term, durable immune responses.
That’s the reason for MOF antigen depot: It allows an intact, dead pathogen to exist in tissue longer, as if it were an infection, to trigger a full-scale immune system response.
For this model, they developed encapsulates and immobilizes an individual bacterium cell in a crystalline polymeric matrix that not only kills the bacterium but also preserves and stabilizes the dead cell against high temperature, moisture, and organic solvents.
In their experiments, researchers used a strain of Escherichia coli. There are no vaccines against any pathogenic strain of this bacterium. Uropathogenic E. coli causes about 80% of all community-acquired UTIs. The study is published in the American Chemical Society’s journal ACS Nano.
When they challenged these mice with a lethal injection of bacteria, after they were vaccinated, almost all of our animals survived, which is a much better performance than with traditional vaccine approaches.
Although the method has not yet been tested in humans, it has the potential to help millions of patients. This work against recurrent UTI would be a significant breakthrough.
Beyond recurrent UTI or urosepsis, researchers believe the antigen depot method could be applied broadly to bacterial infections, including endocarditis and tuberculosis.
Vaccine technology is about two centuries old, and it has evolved amazingly little. They hope platforms can open up using existing, well-studied pathogens to create more directed and engineered immune responses.
Source: Medindia
