Prevention of E. coli Urinary Tract Infection by Vaccination
Escherichia coli (abbreviated as E. coli) are a large and diverse group of bacteria found in the environment, food, and in the intestines of both people and animals. Most strains of E. coli are harmless but some can cause diarrhea, while others cause urinary tract infections (UTI), respiratory infections and other illnesses.
E. coli in urine (called uropathogenic E. coli) are a common cause of UTI and are responsible for more than 85% of UTIs. UTIs rank second only to respiratory infections in their incidence in the US with roughly 11 million physician visits per year, and 130 to 175 million are diagnosed worldwide. Direct health care costs related to uncomplicated UTIs in the US are estimated to be around $2 to $5 billion per year. UTIs also can lead to more severe illnesses, such as pyelonephritis (kidney infection), bacteremia (bacteria in the blood), and sepsis (presence of harmful bacteria and their toxins in the blood or tissues).
Antibiotic treatment, typically with trimethoprim / sulfamethoxazole (Bactrim) or ciprofloxacin, is generally effective. However, documentation of increasing antibiotic resistance, allergic reaction to certain pharmaceuticals, alteration of normal gut flora, and failure to prevent recurrent infections represent significant barriers to treatment. Approximately half of all women will suffer a UTI, and about 25% of those will suffer recurrent UTI. The unmet clinical need is obvious.
One product, Uro-Vaxom (OM Pharma) is currently marketed in Europe, Canada, and other countries. Uro-Vaxom, indicated for prevention of acute UTI, consists of extracts of 18 uropathogenic strains, packaged into a once-daily oral tablet. A full course of vaccine requires three months to complete. A meta-analysis of 5 studies showed that Uro-Vaxom was clinically superior to control (placebo) with respect to the reduction of the frequency of UTIs. However, the studies were not well-controlled; it was hard to know from the publications whether the patients were on antibiotics or not.
Solco-Urovac, a polymicrobial mixture of heat-killed uropathogenic E. coli, comprises 6 of the 10 strains in the suppository vaccine. This vaccine, developed as a product similar to Uro-Vaxom, is being tested in humans at a university in Georgia.
Urvakol / Urostim are products of a Czech and Bulgarian collaboration. The investigators are seeking approval for a formulation of weakened uropathogens in an oral tablet. Urvakol and Urostim contain strains of E. coli, P. mirabilis and E. faecalis, but Urvakol also includes a strain of Pseudomonas aeruginosa, whereas Urostim contains K. pneumoniae. Both have shown immunostimulating activity but the ability of either vaccine to prevent recurrent UTI has not been established.
Swiss scientists published a study describing an oral medicine that targets the protein (FimH) that helps E. coli stick to the inside of the bladder, which is what causes a UTI. Targeting FimH is not the only option. Researchers in the US published a study that showed an immune-boosting agent can boost the body’s ability to resist E. coli from taking hold in the urinary tract.
FimCH which is made of E. coli type 1 fimbrial adhesion (cell-surface components that facilitate adhesion, called FimH) and a protein called FimC. This parenteral vaccine candidate has shown protective efficacy in several animal models (mice, monkeys) and clinical development is in progress.
Most recently, a phase 1 trial of an experimental 4-strain E. coli vaccine found it was safe and produced a strong immune response against all vaccine serotypes for UTIs in women. Further studies of higher doses and different formulations are needed and Phase 2 studies have been initiated.
UTI caused by E. coli is a substantial economic and societal burden. Controlling these infections may someday become a reality and provide an important alternative to the use of frequent or long-term antibiotics.
