A pill-based vaccine prevents urinary tract infections in mice | Tech Reddy

Biomedical engineers at Duke University have developed a tablet-based vaccine against urinary tract infections that dissolves quickly when placed under the tongue. The new treatment may offer an easy and practical alternative to the high-dose, oral antibiotics that are the current standard of care for UTIs.

The findings appeared online in the journal Nov. 23 Science Advances.

Urinary tract infections occur when bacteria infect the urethra, bladder, urethra, or kidneys. More than half of all women experience UTIs, and they pose a significant risk to patients requiring catheters. While UTIs often cause pain and discomfort, if the infection reaches the kidneys, organ damage and even sepsis can occur.

These infections can be treated with oral antibiotics, but some patients face recurrent UTIs that require prolonged, repeated, and sometimes expensive antibiotic use. Long-term use of antibiotics can have a negative effect on the patient’s microbiome, as antibiotics kill off beneficial bacteria and allow the proliferation of antibiotic-resistant bacteria. Today, many strains of bacteria that cause UTIs have become resistant to several antibiotics commonly used to treat these infections.

To solve this problem, a team of collaborators including Joel Collier, Theodore Kenny, a professor of biomedical engineering at Duke University, and Sean Kelly, who completed the work with a Ph.D. A student in Collier’s lab has developed a vaccine that can be absorbed under the tongue and activate primary immune cells to specifically attack the bacteria that cause UTIs.

“Previous literature has shown that drugs absorbed through the sublingual mucosa induce an immune response, particularly in similar mucosal tissues throughout the body,” said Kelly, now a postdoctoral fellow at Johns Hopkins University. “This was important because one of the challenges in developing a vaccine for UTI is that you have to induce an immune response in both the blood and the urinary tract, and intramuscular injections often don’t produce strong responses in mucosal areas.”

“Also, there are many barriers to easy vaccine delivery. You often need refrigeration, trained personnel to administer the shots, and supplies like needles,” Kelly said. “But the delivery method of the tablet offers a solution to many of these problems. It can be stored at room temperature without any problems. The hope is that the patient will take it out of the package, put it under the tongue and in several places. Seconds later, it’s gone and the patient can go about their day. .”

The mucous layer under the tongue is difficult to penetrate because mucus is designed to prevent large molecules, viruses, and other materials from entering the body. But Collier’s lab specializes in developing biomaterials that self-assemble into useful structures, such as nanoparticles, nanofibers and gels, tailored to activate key cells of the immune system. The team discovered that these structures can add mucus-resistant modifications that allow them to easily pass through the mucosa.

After finalizing the sugars and other structural components needed for a fast-dissolving, vaccine-delivery pill, the team began researching how to specifically target UTI-causing bacteria.

“Sean identified certain proteins that are overexpressed in a type of bacteria called uropathogenic E. coli, which commonly causes UTIs,” Collier said. “This gave us a precise target for the immune cells to attack.”

The team woven E. coli proteins into mucus-permeable nanofibers. Once this structure is absorbed, the added bacterial proteins activate immune cells, giving them specific instructions to kill bacteria in the blood and urinary tract.

“The efficacy of the vaccine delivered via tablet is comparable to that of antibiotics, and we found that the antibody responses elicited by the nanofibrous materials can be sustained throughout the life of the mouse and very durable, so we hope that the protection against UTIs will be the same in the long term,” Collier said. “Sean and the team also performed microbiome analyses, and they found that the gut microbiome of the mouse models was less disrupted than antibiotics.”

The team will continue to refine the model as Collier and his collaborators wonder if the vaccine could be used to reduce or prevent UTI recurrence. They also plan to study additional disease models where a sublingual vaccine delivery mechanism would be particularly useful. Many of these diseases, including gonorrhea and chlamydia, also involve the genitourinary tract and face problems of antibiotic resistance.

Although the team is excited about the long-term UTI protection results, they are optimistic about the new possibilities with sublingual vaccine tablets.

“Especially in the wake of COVID, it’s becoming increasingly clear that vaccines will become more and more a part of our lives, so we need affordable vaccines that can be easily replicated,” Collier said.

“Current vaccines depend on continuous refrigeration, requiring significant infrastructure that is not available in large parts of the world. Tablet technology can be delivered much more equitably because it avoids dependence on refrigeration,” Collier said. “If we’re successful, anyone can get the vaccine, whether they’re close to a large hospital system or not. We’re far from that reality, but we’ll continue to work in that direction.”