Developing a novel vaccine to treat Urinary Tract Infections

By teaching the body’s own immune system to quickly detect and defend against bacteria, a new vaccine may reduce and prevent recurring Urinary Tract Infections and the complications they can trigger. 

Every year around 250,000 Australians develop a Urinary Tract Infection (UTI), a common condition that affects one in three women and one in twenty men in their lifetime. Though uncomplicated UTIs usually respond to antibiotic treatment, antimicrobial resistance is increasing, particularly in recurrent UTIs. So, there is a pressing need for treatment alternatives for these complex urinary tract infections. Rising to this challenge, a new research project led by Professor Iain Duggin from UTS, has been approved to develop a novel vaccine targeting UTIs. The vaccine will employ mRNA technology similar to that used in COVID-19 vaccines. Funding has been provided through an MRFF (Medical Research Future Fund) Global Health Initiative grant. Support is also being provided by other partners, including the Office for Health and Medical Research (OHMR).  

OHMR’s Advanced Therapeutics team are providing input to the project by offering support via their expertise in policy development and clinical translation for research, clinical trials, biomanufacturing and workforce development. This ‘in kind’ contribution to research involving RNA-based vaccines is part of an ongoing commitment by NSW Health to advancing a world-leading RNA ecosystem in NSW.  

Drawing on extensive expertise

The project will involve a collaboration between the University of Technology Sydney, the CSIRO and the UNSW Sydney. ‘We have Bioinformaticians supporting the vaccine design, immunologists supporting the vaccine response and efficacy testing, and clinicians supporting the patient-centred research and design of clinical trials,” says Professor Iain Duggin, Deputy Director of the Australian Institute for Microbiology and Infection at UTS and lead investigator on the UTI vaccine project “We also have biochemists and biomanufacturing experts for synthesising and formulating vaccine components and testing/quality control of the formulations.” It is hoped that clinical trials on the vaccine will take place in the next three years. 

Improving treatment options and outcomes

“Women are a big population group impacted by UTIs, especially during the hormonal changes of peri-menopause and menopause,” says Duggin. “Patients with spinal cord injury who need to use catheters (tubes placed into the bladder) for extended periods are also at greater risk: UTIs are one of the leading causes of death and hospitalisation in people with spinal cord injury.” This research will include input from these and other patient consumer groups. 
 
UTI impacts and complications

UTIs are one of the most common bacterial infections treated by GPs. “Infections of the lower urinary tract (mostly the bladder) can be very painful and also debilitating,” says Duggin. “Recurrent UTIs can impact the urethra as well and greatly increase the risk of dangerous kidney and bloodstream infections, which may lead to chronic kidney or urinary tract diseases.” 
 
A species of bacteria called Escherichia coli (E. coli) and other gram negative bacteria are the main cause of UTIs. They generally have reservoirs in the gut, where they are largely harmless, but can migrate to other places in the body including the urinary tract. As a result of growing microbial resistance, UTIs do not always respond to antibiotic treatment.  

Stimulating immune memory 

One of the problems with UTIs and recurrent UTIs is that repeat exposure to the bacteria that cause their infections does not seem to improve immune memory sufficiently in many patients. “Without immune memory, it is difficult for the body to mount a stronger defence to the next exposure to that bacteria so that the person does not develop a UTI or at least develops a less virulent infection,” says Duggin. “The bacteria that cause UTIs mostly triggers the innate immune system. This response includes inflammation and shedding of the lining of the urinary tract to physically expel the bacteria. Our team hopes that the vaccine we are developing will address this by triggering a targeted response to help the body develop a specific immune memory which can be harnessed to better defend against the bacteria that cause UTIs.” 
 

Building on mRNA advances 

“In our work on a UTI vaccine we are using mRNA messenger technology that has been under development for more than 30 years but was fast-tracked and highly effective during the COVID-19 pandemic,” Duggin explains. “We expect that the vaccine will specifically target the surface of the bacteria that invade the bladder or other surfaces of the urinary tract. This will assist the immune system to recognize the E. coli bacteria and quickly clear it from the site of the infection.” 

 The aim of the vaccine is to prevent UTIs in patients susceptible to recurring UTI. It is hoped that the vaccine will also reduce UTI complications or infection recurrence by clearing the bacteria from other places in the body, such as the bloodstream and kidneys. 
 

Tailored and targeted vaccines

The UTI vaccine project aims to tailor vaccines to different patient groups. “We have about 12 different formulas that we want to develop and test on human cells in the lab,” Duggin says. “Due to decades of research, the basic chemicals that make up mRNA vaccines are pretty set now – it’s the sequence of the mRNA that mostly changes. We will be testing out each of the 12 different formula but we know that mRNA vaccines are generally very safe.”