A research paper published in Science Advances suggests the possibility of UTI prevention through a sublingual vaccine. The paper, released in November 2022, details the success of the vaccine in mice and rabbits, indicating that there is hope for human solutions. Researchers from Duke University in the USA believe that their vaccine, which targets the uropathogenic Escherichia coli (UPEC), the cause of 80% of uncomplicated UTIs, can be a gentler alternative to antibiotics.
The authors suggest that the “major health problem” of UTIs affects “millions” every year. Specifically, 50% of all women are believed to suffer from a UTI in their lifetime. The current option for managing this is “long-term antibiotic use”.
There are risks associated with antibiotic taking, particularly for gut microbiota. The study describes how, in addition to drug-specific adverse effects, prolonged antibiotic use alters the microbes’ “metabolic activity, gene expression, and protein synthesis”, as well as reducing “diversity” as a whole. However, risks are not limited to the direct effects of the drugs, but the growing resistance to them. Modelling suggests that by 2050, “current practices would result in 10 million additional deaths per year by infection”.
“Antibiotic resistance compounds the effects already associated with prolonged antibiotic resistance use, making it likely that safe, effective treatment and prevention of UTIs will become increasingly challenging.”
UPEC have become “increasingly resistant” to common antibiotics. Therefore, the study infers an “urgent unmet need” for a “more effective form of UTI prevention”.
With this “unmet need” in mind, the authors considered the possibility of a vaccine that “raises protective, long-term antibody responses against UTI-causing bacteria”. With no such vaccine available, and “significant” barriers to its development, their task seemed a “major challenge”.
“An ideal vaccine candidate would elicit immune responses that are specific to UTI-causing bacteria to avoid adverse effects to the microbiota while also targeting a broad range of UTI-causing pathogens.”
The assumption that protection against UTIs relies on “systemic responses in the blood and mucosal responses in the urogenital tract” suggest that the vaccine should:
- Be able to raise simultaneous responses against multiple highly specific and carefully selected epitopes targeting only pathogenic bacteria
- Be able to elicit mucosal responses
- Feature efficient dosing regiments that facilitate compliance and minimise cost
With a supramolecular approach the researchers assembled multiple selected B cell epitopes from UPEC into “sublingually immunogenic nanomaterials”. This method of administration is “known to elicit antibody responses in the urogenital tract”, but it is hard to “raise robust immune responses against short peptide epitopes” this way, as peptides are “poorly immunogenic via the oral mucosa”. However, they were able to demonstrate with model epitopes that supramolecular peptide nanofibers “bearing polymer modifications modulating mucus adhesivity” can raise “strong systemic and mucosal antibody responses”.
In the study the authors mine the “unique advantages” of their platform. In mice the vaccine elicited “robust anti-UPEC antibodies that were not cross-reactive against commensal E. coli. Furthermore, it was “as effective as high-dose oral antibiotics” at protecting mice from “lethal challenge with UPEC”.
“We report a novel vaccination strategy, enabled by biomaterial design, that provides long-lasting, antibiotic-level efficacy against UPEC.”
As the tablet can be self-administered and is stable at room temperature, it is easy to store, deliver, and administer. This has the potential to “lower costs of vaccine delivery”, suggests Sean Kelly, an author of the paper. Co-author Professor Joel Collier intends to “conduct biodistribution and safety studies” before clinical trials. His team are “actively seeking partners to accomplish this”.
For more on the benefits on novel delivery methods get your tickets to the World Vaccine and Immunotherapy Congress in San Diego next week!