Two new antigens have been identified for use in a urinary tract infection (UTI) vaccine in research presented at ASM Microbe 2016.

Researchers from the University of Michigan in Ann Arbor developed a vaccine to target siderophores, which are small molecules produced by bacteria. Siderophores capture iron from the environment to deliver the nutrient metal to the bacterial cell during an infection, and pathogen-associated siderophores evade host immune defenses to enhance bacterial virulence.

Approximately half of women in the United States will have a UTI in their lifetime, and 1 in 40 women will have further recurrent infections. Uncomplicated UTI is primarily caused by uropathogenic Escherichia coli (UPEC), which gains access to the bladder through periurethral colonization and ascension in the urethra. Infections are typically resolved with standard antibiotic regimens, but with infections that are not restricted, the bacteria could ascend to the kidneys and cause pyelonephritis, sepsis, or death. In addition, frequent or continuous antibiotic treatment used to treat recurrent UTI infections will eventually cause increased antibiotic resistance and there is currently no UTI vaccine approved in the United States.


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Recent data have suggested that immunization with siderophore receptor proteins was effective in a murine model of UTI. However, the proteins have poor solubility in aqueous solutions, which limits their practical utility. But because their cognate siderophore ligands are water soluble, the researchers hypothesized that pathogen-specific siderophores would be effective for a vaccine.

The researchers vaccinated mice with 2 UPEC siderophores conjugated to immunogenic carrier proteins, both individually and in combination. They found that vaccination with individual siderophores reduced bacterial burden in the urine and kidneys. Co-immunization also decreased bacterial burden in the urine 14-fold and decreased bacterial burden in the kidneys 126-fold.

Overall, the vaccines caused a B cell-mediated immune response that targeted bacterial siderophores and protected against UTI.

Reference

Mike LA, Smith SN, Sumner C, Mobley HLT. Session 014. Siderophore vaccine conjugates stimulate adaptive immunity to protect against Escherichia Coli urinary tract infections. Presented at the American Society for Microbiology Microbe 2016; June 16-20, 2016; Boston.