Researchers at UT Dallas are investigating the use of whole-cell vaccines to fight urinary tract infection (UTI). It is part of an effort to tackle the increasingly serious issue of antibiotic-resistant bacteria.
Dr. Nicole De Nisco, assistant professor of biological sciences, and Dr. Jeremiah Gassensmith, associate professor of chemistry and biochemistry, recently demonstrated the use of metal-organic frameworks (MOFs) to encapsulate and inactivate whole bacterial cells to create a “depot” that allows the vaccines to last longer in the body.
The resulting study, published in print Nov. 23, 2021, in the American Chemical Society’s journal ACS Nano, showed that in mice this method produced substantially enhanced antibody production and significantly higher survival rates compared to standard whole-cell vaccine preparation methods.
“Vaccination as a therapeutic route for recurrent UTIs is being explored because antibiotics aren’t working anymore,” De Nisco said. “Patients are losing their bladders to save their lives because the bacteria cannot be killed by antibiotics.”
If not successfully treated, a UTI can lead to sepsis, which can be fatal.
Recurrent UTI, De Nisco said, is primarily regarded as a women’s health issue, and although it’s common – especially in postmenopausal women – it’s something many women don’t talk about a lot.
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 challenge.
“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,” Gassensmith said.
“That’s the reason for our MOF antigen depot: It allows an intact, dead pathogen to exist in tissue longer, as if it were an infection, in order to trigger a full-scale immune system response.”
In their experiments, the 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.
“When we challenged 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,” Gassensmith said.
Although the method has not yet been tested in humans, De Nisco said it has the potential to help millions of patients.
“This study on UTI was a proof of concept that whole-cell vaccines are more effective in this extreme, lethal-sepsis model,” De Nisco said. “Showing that this works against recurrent UTI would be a significant breakthrough.”
De Nisco’s continuing exploration of how UTIs progress and recur in older women is funded by a $1.3 million grant from the National Institutes of Health. The researchers also are funded by grants from the National Science Foundation and The Welch Foundation.
–Stephen Fontenot