Researchers have developed a promising new vaccine against urinary tract infections that kills and then preserves offending bacteria long enough for the immune system to produce a long-term, durable response.
With antibiotics becoming increasingly ineffective at staving off UTIs, the vaccine, which uses a metal-organic framework to catch and contain whole bacterial cells, may be the best way to spare patients — and their bladders — from an unnecessary ordeal. The study, published in the journal ACS Nano, showed that mice treated with the vaccine experienced enhanced antibody protection and higher survival rates than those given standard whole-cell vaccines.
“Vaccination as a therapeutic route for recurrent UTIs is being explored because antibiotics aren’t working anymore,” said Nicole De Nisco, an assistant professor of biological sciences at the University of Texas at Dallas. “Patients are losing their bladders to save their lives because the bacteria cannot be killed by antibiotics or because of an extreme allergy to antibiotics, which is more common in the older population than people may realize.”
Recurrent UTIs are more common in women — particularly post-menopausal women — than men and is generally viewed as a women’s health issue even though it is seldom discussed, De Nisco said. Canadian women make around 500,000 visits per year to doctors seeking treatment for a UTI, according to the Kidney Foundation. The issue generally arises when E. coli living on the skin outside the body manages to enter the urethra, travel to the bladder and cause an infection. UTIs are more common in women than men because they have shorter urethras, meaning bacteria does not have as far to travel to cause problems.
Symptoms of a bladder infection — the most common form of UTI — include not being able to urinate despite feeling an urgent need to do so, a burning sensation during urination, cloudy or foul-smelling urine or lower abdominal pain. If symptoms do not fade within a couple of days, a urine test and antibiotics may be prescribed. Without treatment, a more serious infection can result if the bacteria migrate from the bladder to the kidney.
“Every subsequent infection becomes more difficult to treat,” De Nisco said. “Even if you clear the bacteria from the bladder, populations persist elsewhere and usually become resistant to the antibiotic used. When patients accumulate antibiotic resistances, they’re eventually going to run out of options.”
Vaccines work by introducing a weakened version of disease-causing germs, known as antigens, to an immune system to stimulate the creation of antibodies. It is more difficult to design a vaccine for bacteria than a virus because they are larger and more complex and it can be difficult to know which biological components will work best as an antigen. For this reason, researchers take a whole-cell approach when it comes to bacteria, even though this approach has its own shortcomings.
“We throw the whole kitchen sink at them because that’s what your body normally sees when it becomes infected,” said Jeremiah Gassensmith, an associate professor of chemistry and biochemistry at the University of Texas at Dallas. “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 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.”
The new vaccine’s metal-organic framework does this by encasing an individual bacterium cell in a crystalline polymeric matrix that kills it and keeps the dead cell safe from high temperatures and organic solvents, giving the immune system time to adapt. The vaccine proved effective in mice models that were infected with a pathogenic strain of Escherichia coli for which there is currently no vaccine.
“When we 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,” Gassensmith said. “This result was repeated multiple times, and we’re quite impressed with how reliable it is.”
The vaccine, which has not yet been tested on humans, could help millions of patients, De Nisco said, and researchers are hopeful it can be adapted to fight other bacterial infections, such as tuberculosis and endocarditis. “We’re working on translating this approach to TB, which is a very different organism, but like uropathogenic E. coli, when it enters the tissue, it stays, and it recurs,” Gassensmith said.
“It requires a new way of thinking about how vaccines should work. Vaccine technology is about two centuries old and it has evolved amazingly little. We hope our platform can open up using existing, well-studied pathogens to create more directed and engineered immune responses.”
Dave Yasvinski is a writer with Healthing.ca