Vaccines

Vaccines are another potential treatment path for UTI away from the usage of oral antibiotics that may be offered. They work by stimulating the immune system.

Vaccines programme the immune system to respond when it encounters an ‘invader’. It encourages white blood cells to respond. When these white cells encounter the trigger (or ‘antigen’), they quickly begin to multiply and release antibodies. Antibodies bind to these triggers, inactivate them, and remove them from our systems.

A vaccine against the diverse range of pathogens that can cause urinary tract infections has proved illusive. Indeed in the development of these vaccines there is the assumption that the causative agent for infection has been identified allowing treatment with a vaccine. A vaccine will need to ensure that there is an effective immune response in the urinary tract and in particular that of the bladder wall mucosa. At present and until there is a greater understanding of how the immune system can be restored to prevent recurrent and chronic infections, for those with chronic UTI vaccines may help alongside antibiotics rather than as a standalone treatment but it is an expensive, unproven adjunct.

A detailed research study published in 2012 in the Expert Review of Vaccines discusses the science behind the need for a vaccine for UTI in light of rising antibiotic resistance.

In 2018 a systemic vaccine literature review was undertaken by Guy’s hospital in London and The University of Oxford. Their conclusions included:

Uro-vaxom

Uro-vaxom, developed and manufactured in Switzerland, contains 18 heat killed inactive strains of e coli and can be taken to treat infections specifically due to e-coli. It has been available since 1988 and marketed and sold in almost 40 countries worldwide, excluding the USA and Canada. Uro-vaxom is available in a capsule format and is taken once a day.

Uromune

Uromune, developed and manufactured in Spain, is composed of heat killed inactive strains of Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris and Enterococcus Faecalis in equal amounts. It is taken under the tongue via a sublingual pineapple flavoured spray.

Urovac

Manufactured in Switzerland by Solco, this is a vaccine containing a mixture of ten uropathogens – six strains of uropathogenic E-coli (UPEC) and one strain each of Proteus mirabilis, Morganella morganii, Enterococcus faecalis and Klebsiella pneumoniae.

What you should know about vaccines for chronic UTI

• These trials and studies are based on patient cohorts with identified urine infection on standard laboratory testing. Patients with embedded bladder wall infections not detected during standard pathology analysis have been excluded due to lack of bacterial identification during the recruitment phase. Some trials were also uncontrolled lacking placebo comparators.
• In using patients with identifiable bacteria, an assumption is made about the bacteria being the causative agent of infection, those with chronic infections may well harbour diverse pathogens in their urine against which a vaccine is ineffective. Designing a UTI vaccine that can be effective against such a diverse pathogen population may prove to be a considerable challenge. An effective vaccine for UTI will need to ensure that there is an effective immune response in the urinary tract and in particular that of the bladder wall mucosa.
• It is worth questioning whether the response of the urinary tract immune system is truly influenced by a vaccine taken orally – in the results these studies found, could other factors have led to an improvement in the number of infections trial participants experienced?
• Much of the understanding of UTI infections and the ability to evaluate vaccine designs have relied on the use of mice. However, like all animal models of human disease, mouse models of UTI are not without limitations. Physiological differences between mice and humans include differences in the urinary tract, such as urine concentration and contents (mouse urine contains more protein and is more concentrated compared with human urine) thus requiring avoidance of direct comparison between human and mouse studies. Indeed, studies comparing bacteria obtained from UTI in the mouse and active human UTI have identified differences, indicating unsurprisingly that artificial infection of the mouse does not directly equate with natural infection in humans.
• The body’s natural defences such as white cells or antibodies find it hard to get through the sticky, protective layer of biofilms thus preventing an immune system response to pathogenic infection causing bacteria.
• At present, vaccines are considered an adjunct alongside standard antibiotic treatment for those with Chronic UTI and not a stand alone treatment.
• Cost and availability. Treatment costs using vaccines are expensive and at present are available through a private secondary consultant such as a urologist on a named private patient basis only. Vaccines are currently not licensed for usage in the USA and Canada.

What next for vaccines?

The Hultgren Laboratory in the US are focusing on developing antibiotic-sparing methods of treatment that focus on the laboratory’s knowledge of adhesins critical in UTIs. They are working to target these adhesins to prevent embedded and biofilm formation by UPEC, Klebsiella, Acinetobacter and Enterococcus during UTIs and/or catheter associated UTIs. The advantage of this approach is that it is beneficial against both antibiotic-resistant and antibiotic-sensitive pathogens.

Their development of Mannosides which neutralises the adhesion function of uropathogenic E-coli bacteria to the bladder wall cells to cause UTI. A mannoside has now been selected for clinical trials in humans in collaboration with Glaxo Smith-Kline. This has led to a phase 1a/1b Mannoside vaccine clinical trial which was completed successfully leading to its allowance by the US Federal Drug Administration for compassionate use in individuals suffering from recurrent UTI who no longer respond to standard antibiotics including last line agents.

Find out about other treatments for chronic UTI.