A Sugar Molecule against a dangerous Hospital Fungus

Researchers have developed a chemically defined approach against the multidrug-resistant hospital fungus Candida auris. A synthetic sugar molecule serves as the basis for a vaccine candidate, protective antibodies, and a prototype for a rapid test.

To the point

• A Growing Challenge: Candida auris is an emerging, multidrug-resistant fungal pathogen that is spreading particularly in healthcare facilities. To date, neither vaccines nor rapid diagnostic methods are available for C. auris.
• Precise Sugar: Researchers have identified a precisely defined sugar structure that corresponds to a component of the C. auris surface. The synthetic β-mannan epitope makes it possible to direct the immune response specifically against the fungus. 
• Three-Pronged Approach: The sugar structure serves as the basis for a vaccine candidate and for protective antibodies. In addition, the researchers used one of these antibodies to develop a prototype for a rapid test to detect multiple Candida species.

Fungi are particularly dangerous hospital-acquired pathogens: they often infect people whose immune systems are already weakened. One challenge is the emerging, multidrug-resistant yeast Candida auris. It was first discovered in Japan in 2009 and has since spread worldwide. To date, there are neither vaccines nor rapid diagnostic methods available. The World Health Organization (WHO) has classified C. auris as a fungal pathogen of critical priority since 2022.

Now, researchers at the Max Planck Institute of Colloids and Interfaces, Freie Universität Berlin, and the Centre for Medical Mycology at the University of Exeter in the United Kingdom have developed an approach that enables multiple strategies against the fungus. At the heart of the approach is a chemically synthesized sugar molecule that mimics a structure on the surface of C. auris. It serves as the basis for a vaccine candidate and for therapeutic antibodies and has also been used in a prototype rapid test.

“Through chemical synthesis, we can precisely replicate individual sugar structures of the fungus and determine which ones the immune system recognizes,” says Peter H. Seeberger, director at the Max Planck Institute and co-author of the study. “This opens up the possibility for us to find a strategy to combat Candida auris.”

The Key Sugar Structure Identified

Developing a vaccine against the yeast C. auris is a particular challenge. Fungal cell walls consist largely of complex sugar structures. These do not exist as uniform structures but differ, among other things, in length and linkage. It is therefore not easy to determine which of these structures the immune system recognizes and triggers a protective immune response.

For this reason, the researchers chemically synthesized the sugar structures in the laboratory. This allowed them to study individual molecules with precisely defined composition and structure. In the process, they identified a promising molecule consisting of four linked sugar building blocks that corresponds to the sugars on the surface of the fungi. It is a β-mannan tetrasaccharide that is recognized by antibodies.

From Sugar Molecule to Vaccine Candidate

To enable the immune system to specifically recognize this particular sugar structure, the sugar was linked to a carrier protein. The combination of sugar and protein is called a glycoconjugate and helps trigger a targeted immune response against the sugar structure.

In the study, an infection model using mice showed that vaccination with the glycoconjugate triggered a specific immune response. The animals produced antibodies that specifically recognized the synthetic sugar structure. In the vaccinated animals, the fungal load in the kidneys and spleen was reduced following infection.

“Our results show that a single, chemically defined sugar structure is sufficient to elicit a targeted immune response against Candida auris and to limit the infection in the animal model,” says Seeberger. “This provides important preclinical evidence of efficacy for this vaccine approach.”

The Same Sugar Enables Both Therapy and Diagnosis

The researchers also developed an antibody that specifically recognizes the sugar structure. In the animal model, this antibody likewise protected the mice from infection, resulting in a reduced fungal load in the spleen of passively immunized mice.

But the sugar structure can do even more: The antibodies can also be used to detect the fungus. The researchers used them to develop a rapid test based on a principle similar to that of a pregnancy or COVID-19 rapid test. The test detects structures on the surface of C. auris and could potentially enable rapid identification of the fungus.

“The fact that the same sugar structure can be used for a vaccine as well as for antibodies and a diagnostic test is particularly interesting. We are thus demonstrating the potential that chemically defined glycans have for infectious disease medicine,” says Seeberger.

The researchers have thus achieved a series of successes: Using a single, chemically defined sugar molecule, they were able to develop a vaccine candidate, identify protective antibodies, and produce a prototype for a rapid test. The results thus combine vaccination, passive immunization, and diagnostics based on a single defined sugar structure.

The findings build on earlier work by the research team, in which synthetic sugar structures from Candida were produced and examined for their immunological recognition. The current study now takes this approach a step further.

The approaches developed are still in preclinical development. The vaccine candidate and the antibodies have so far been tested in animal models. The rapid test is also initially a prototype. Further studies are required before it can potentially be used in humans.