ETH Zurich researcher aims to prevent urinary tract infections with a vaccine
Every second woman and every eighth man suffer from urinary tract infections. These are painful and can recur with serious health consequences. Pioneer Fellow Giorgia Greter has a solution.
In brief
- The bacterium E. coli causes urinary tract infections for many people. Women are particularly affected.
- The harmful bacteria hide from the immune system under a capsule. Infections often must be treated with antibiotics, which promotes resistance.
- Giorgia Greter's start-up, Baxiva, is developing a vaccine that will make these bacteria visible to the immune system – it combines polysaccharides from the bacterial surface with an immune-stimulatory protein.
Giorgia Greter could have been sitting in one of these minimalist, but elegant offices of a venture capital company – analyzing the potential of start-ups and novel technologies to disrupt markets. She could have, as well, not be studying business plans, but rather petri dishes in a lab – forging an academic career answering some of life’s fundamental questions.
Instead, the 29-year-old researcher is enthusiastically talking about the start-up she is building on the same campus where she completed her doctoral studies: ETH Zurich’s H?nggerberg.
The start-up, Baxiva, is developing a vaccine to prevent urinary tract infections (UTIs). Such infections are extremely unpleasant. They begin with painful and frequent urination. Sometimes spasmodic pain floods the abdomen and occasionally blood clouds the urine. These infections can be very difficult for the body to fight off. If left untreated, the infection can progress to the kidneys, and in rare cases, into a life-threatening bloodstream infection.
More and more resistances against antibiotics
“Nearly one out of two women will - at least once in her lifetime - get a UTI. They also occur in one out of eight men, who are prone to them especially as they get older”, explains Greter. Some will be lucky enough to rarely contract such an infection. But for many, especially women, it is an all-too-familiar problem that keeps coming back.
Greter points out how common these infections are and how negatively they impact productivity and quality of life. Studies have shown that UTIs not only cause pain and health problems, but also anxiety and feelings of guilt: people with recurring UTIs are fearful of their next infection.
As is one person in Greter’s closer social circle. They are suffering from recurring UTI and, therefore, have to take antibiotics several times per year.
Treating all these infections with antibiotics, which currently is the only effective treatment, leads to a problem: “More and more E. coli develop resistance against antibiotics,” says Greter. Drugs that have been around for decades no longer work reliably. And this problem is growing rapidly.
From the intestinal tract to the urinary tract
E. coli, short for Escherichia coli, is a bacterium Greter is very familiar with: she received the ETH medal for her doctoral studies in Quantiative Microbial Ecology investigating E. coli in the gut.
Fungi or viruses can also trigger a urinary tract infection. However, E. coli is by far the most frequent culprit.
The bacterium is naturally present in our intestines, which is healthy. Most of are not even able to cause infections. “But some harmful strains have evolved specialized tools for invading the urinary tract”, says Greter. “They have adhesins to latch onto the delicate lining of the urethra and avoid being flushed out during urination. They have toxins that break open our cells to access nutrients, and a protective polysaccharide capsule that makes these bacteria nearly invisible to the immune system,” describes Greter The scientist has a knack explaining complex things in simple terms.
“It’s a massive problem to solve.”Giorgia Greter
This will be important to fund the company. Vaccines have a long and cost-intensive road to being sold in clinics. Greter estimates that developing their vaccine will need more than one billion Swiss Francs in investment over 10-15 years before it could be available at a pharmacy or a doctor’s office.
This is a big investment, she admits, “but it’s a massive problem to solve, and this testing is an important process to establish that a vaccine is safe and effective before it is sold.” The project is off to a good start, their application to the Swiss innovation agency, Innosuisse, has just been approved.
Teaching the immune system to see the bacteria’s capsule
But what exactly is Greter's approach? She says: “Our immune system is always on the lookout for bacteria that invade our body and its usually very good at killing them, otherwise we wouldn’t be here.” But these harmful E. coli bacteria hide from our immune system under their polysaccharide capsule. “What our vaccine does is to teach the immune system to recognize the capsule and attack”, she explains.
Developing such a vaccine is no simple task – and this is where Baxiva’s technology comes into play. “To teach the immune system to recognize the capsule we need to glue the polysaccharide together with an immune-stimulating protein and inject this combination into the body.” This is a well-known type of vaccine called a glycoconjugate, glycan being another word for describing polysaccharides.
For a long time, it was considered impossible to develop a glycoconjugate for E. coli because their capsules are made of many different complex polysaccharides, each with its own complex chemistry.
A vaccine with less side-effects
In fact, Giorgia’s colleagues in the Mucosal Immunology Lab, Emma Slack, Tim Keys and Christoph Rutschmann have been researching E. coli surface polysaccharides for years. Greter explains, “The breakthrough came when our group began working together with chemists in the Bode Group. We identified a specific chemical handle on all E. coli polysaccharides and our colleagues in chemistry designed a ‘linker’, the perfect glue, for sticking these polysaccharides onto a protein.”
The advantage of such a vaccination is that the harmless bacteria are not affected. And because this vaccine contains precisely defined components, it is expected to have less side-effects compared to vaccines that inject whole killed bacterial cells.
Other vaccines need a booster
Once you have been vaccinated against E. coli, you should not get another infection, and certainly not a bloodstream infection, says Greter.
This differs from vaccines that are already available in some countries. There is a urinary tract infection vaccine, for example, where you have to take an oral capsule containing a cocktail of killed bacteria regularly. It was recently the subject of a study which found that almost half of those taking the capsules will still have UTI after nine years.
Another injected vaccine needs multiple doses for basic immunization and needs to be renewed every year. It also has unpleasant side effects such as flu-like symptoms and, in rare cases, cardiovascular problems. Moreover, its efficacy remains controversial.
Exchange in the laboratory
These types of vaccines are based on a different technology - inactivated native components of E. coli are inoculated in these cases. Without the technological advances of Baxiva, these vaccines can only induce immune responses against bacterial structures that are normally hidden under the thick capsule being targeted by Baxiva’s vaccines.
The development of the Baxiva vaccination technology shows that often science does not work in a linear fashion. It also illustrates how important human interaction is for progress. During Greter's doctoral studies, Tim Keys and Christoph Rutschman, who later became her two co-founders, were conducting research in the same laboratory.
“We had been working on very different projects and never collaborated. But the way that the Mucosal Immunology group operates means that we always saw and discussed what the other was working on,” Greter recalls.
Reorientation with an entrepreneur program
At that time, like many doctoral students, Greter asked herself the question: Academia or free enterprise? “I wanted to evaluate all my options. So, I went to informational events organized by consulting firms, pharmaceutical and venture capital companies.” At the latter, Greter believed she could put her scientific and analytical skills, as well as her drive and determination to make a difference, to good use.
Joining a program at ETH Zurich and the Universities of Zurich and Basel further cemented her career objectives. At “Feminno,” a programme specifically developed to promote female researchers into the innovation sector, Greter realized that she has a flair for entrepreneurship.
Her colleagues, Keys and Rutschmann, who are familiar with her entrepreneurial aspirations and her ability to build bridges between science and business - after all, they work side by side – knew immediately she was the right person to lead the new start-up. Since 2023, they have been working together on their ETH start-up, Baxiva.
Race against the competition?
They have already tested the vaccine in mice – with, so far, promising results. Now, they are looking for a specialist who can produce clinical-grade vaccine batches in the laboratory. Then the cascade of clinical trials and testing will follow.
There are other companies with technologically different vaccination solutions for UTIs that are already in the test phase. “The market barrier for the first mover is lower. So, we need proof that we will achieve a higher coverage or better protection,” says Greter. And adds with a confident smile: “The literature strongly suggests that our approach of targeting the glycan capsule is the right one.”