Novel Tablet-based Vaccine for Urinary Tract Infections

A tablet-based vaccine for urinary tract infections (UTIs) that rapidly dissolves when placed under the tongue has been developed by biomedical engineers at Duke University. The novel therapy may provide a simple and useful alternative to the high-dose oral antibiotics that are now the gold standard for UTI treatments.

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What are Urinary Tract Infections

When germs invade the urethra, bladder, ureters, or kidneys, urinary tract infections develop. UTIs affect more than 50% of women. They represent a serious risk to patients who need catheterization. UTIs frequently result in pain and discomfort, but if the infection spreads to the kidneys, it can also result in organ damage and even sepsis.

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Recurrent UTI and Prolonged Antibiotic Use

Oral medicines can treat these infections, but some patients experience recurring UTIs that necessitate lengthy, frequent, and occasionally pricey antibiotic therapy. Due to the medicines' ability to kill both beneficial and harmful bacteria, prolonged antibiotic usage harms the patient's microbiome by fostering the growth of bacteria that are resistant to antibiotics. Many of the standard medications used to treat these infections are no longer effective against many strains of the bacteria that cause UTIs today.

Sean Kelly, a former PhD student in the Collier lab who worked on this project, and a group of collaborators, led by Joel Collier, the Theodore Kenney Professor of Biomedical Engineering at Duke, developed a vaccine that can be absorbed under the tongue and activates critical immune cells to precisely attack UTI-causing bacteria.

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Developing Vaccine for UTI

“There was previous literature that showed that drugs absorbed through the mucus membrane under the tongue could trigger an immune response, especially in similar mucosal membranes throughout the body,” said Kelly, now a post-doctoral fellow at Johns Hopkins University. “This was important, because one of the challenges for developing a vaccine for UTIs is that you need to trigger an immune response in both the blood and in the urogenital tract, and the intramuscular shots generally do not trigger strong responses in those mucosal areas. Additionally, there are a lot of barriers to easy vaccine delivery. You often need refrigeration, you need to train personnel to administer the shot, and you need materials like needles. But the tablet delivery method offers a solution to a lot of these problems. It can be stored at room temperature without any issues. The hope is that a patient could pop it out of a package, put it under their tongue and in a few seconds, it’s gone, and the patient can go on with their day.”

It can be challenging to penetrate the membrane layer behind the tongue since mucus was developed to stop big molecules, viruses, and other substances from entering the body. However, the Collier lab specializes in creating biomaterials that spontaneously self-assemble into practical forms like nanoparticles, nanofibers, and gels that may be tailored to stimulate certain immune system cells. The group discovered that they could modify these structures to make them mucus-resistant, which makes it simple for them to pass through the mucosal layer.

The team began looking into how to specifically target UTI-causing bacteria after deciding on the sugars and other structural elements required in a rapidly dissolving, vaccine-delivery tablet.

“Sean identified certain proteins that appeared frequently in a type of bacteria called uropathogenic E. coli, which causes most UTIs,” said Collier. “That gave us a clear target for the immune cells to attack.”

The group incorporated E. coli proteins into their nanofibers that penetrate mucus. Once this structure has been taken up, the bacterial proteins that have been combined into it activate immune cells and give them instructions to kill the bacteria in the blood and urogenital tract.

“The efficacy of the tablet-delivered vaccine was comparable to antibiotics, and we have found that antibody responses raised by the nanofiber materials can be very durable, lasting for the lifetime of a mouse, so we are hopeful that protection from UTIs will be equally long-lasting,” said Collier. “Sean and the team also conducted microbiome analyses, and they found that there was significantly less disruption to the gut microbiome of the mice models than what we see with antibiotics.”

Collier and his colleagues are interested in finding out if the vaccination can be used to lessen or perhaps prevent UTI recurrence, therefore the team will continue to develop their model. Additionally, they intend to investigate different disease scenarios where the sublingual vaccine delivery system may be particularly beneficial. Numerous of these illnesses, such as chlamydia and gonorrhea, also affect the urogenital tract and struggle with antibiotic resistance.

The team is encouraged by the potential opportunities presented by the sublingual vaccine pill in addition to being thrilled with the results for long-term UTI protection.

Especially after COVID, it is becoming clear that vaccines are increasingly going to be part of our lives, so we need more accessible vaccinations that can be repeated easily,” said Collier. “Current vaccines, with their dependence on continuous refrigeration, require substantial infrastructure that is not available in vast parts of the world. The tablet technology can be much more equitably delivered because it avoids this dependence on refrigeration,” Collier said. “If we are successful, anyone could receive the vaccine, whether they’re close to a large hospital system or not. We’re a ways off from that reality, but we continue to work in that direction.”

Source-Medindia