Many antibacterial and antifungal therapeutics target the cell wall, which is primarily composed of large polysaccharide chains. [1] Although the overall structures of these polysaccharides are relatively well characterized, the main challenge lies in extracting highly purified saccharide fragments that enable precise identification of their specific epitopes or antigenic determinants. Even minor structural variations in these polysaccharides can lead to a loss of antibody recognition, making the accurate mapping of epitopes complex.
Additionally, culture approach to obtain the polysaccharides for therapeutic development doesn’t guarantee success, as producing the correct capsular polysaccharide in adequate quantities demands meticulous process optimization. [2] Fragile polysaccharides often degrade during extraction procedures, which has led researchers to increasingly pursue synthetic carbohydrate alternatives.
Candida: An Old Foe Without a Vaccine
Invasive infections caused by yeasts of the genus Candida, including bloodstream infections, affect more than 1.5 million people globally each year and result in approximately one million deaths. Candida species are also among the leading causes of nosocomial bloodstream infections, ranking as the fourth most common in intensive care unit patients. [3] Currently, there is no available vaccine for the Candida sp. Additionally, the population at risk for Candida infections has grown, accompanied by a rise in breakthrough invasive candidiasis cases. The emergence of C. auris further complicates management and prevention due to its drug resistance and rapid transmission in healthcare settings. [4]
Architecture and Molecular Composition of the Candida Cell Wall
The Candida cell wall, which accounts for roughly 80% of the total cell mass, is composed primarily of polysaccharides. The outer layer mainly contains highly mannosylated glycoproteins, while the inner layer consists of chitin—an unbranched homopolymer of N-acetylglucosamine (GlcNAc)—and β-(1,3)- and β-(1,6)-glucans (Glc). [6] They have evolved several immune evasion strategies, including the masking of β-(1,3)-glucan and chitin, secretion of effector proteins that modulate host immune responses, and production of immunosuppressive molecules, which can impair or induce apoptosis in immune cells.
Adapted from Reuber, E. E. et al. Glycan microarray analysis of Candida-related antibodies in human and mice sera guides biomarker discovery and vaccine development. Proc. Natl. Acad. Sci. 122, e2505340122 (2025)
Mannans are considered the most important antigens for humoral immune responses, as they constitute a major component of the Candida cell wall and are among the primary antigens circulating during infection. Although β-glucans are more abundant in the fungal cell wall than mannans, they typically elicit a weaker immune response. One possible explanation for this phenomenon is the shielding effect of N-mannans, which mask most of the β-glucan from immune recognition.
Uncovering the Key Epitopes of Candida
In a recent study from the Max Planck Institute of Colloids and Interfaces (Potsdam, Germany) led by Prof.Peter H. Seeberger, the researchers investigated whether Candida-related antibodies could be detected from patient serum using glycan microarrays containing synthetic glycans. [5] They explored sera from patients exposed to the 7 most common Candida species that are ranked as critical or high priority pathogens according to the World Health Organization (WHO). [4]
In the study, the researchers employed chemically synthesized, structurally defined glycans that were immobilized onto arrays. Using serum samples from infected patients as well as yeast-infected mouse models, they identified three lead epitopes with strong potential for translational applications: a mannotetrasaccharide (α-1,2Man–α-1,2Man–α-1,2Man–α-1,2Man), a mannopentasaccharide containing both α-1,2 and α-1,3 linkages, and a β-glucan pentasaccharide featuring β-1,3 and β-1,6 branches. These glycan motifs were consistently elevated in serum samples from infected cohorts. Moreover, antibody production against the β-(1,3)-mannose monomer appeared to be unique to Candida krusei, suggesting its potential as a specie-specific biomarker.
Although the number of analyzed samples is limited, these findings collectively provide valuable insights that could guide the design of glycoconjugate or monoclonal antibody–based vaccines targeting species-wide Candida infections and support the development of efficient culture-independent diagnostic tools.
Turning glycan complexity into therapeutic opportunity
This work highlights the challenge of identifying relevant carbohydrate epitopes for infectious diseases. Despite extensive research on Candida species, there are still no broadly effective vaccines, antibody therapeutics, or rapid diagnostic systems that cover multiple species. The development of well-defined carbohydrate epitopes remains limited by the structural complexity and vast diversity of fungal or bacterial polysaccharides.
Asparia Glycomics is uniquely positioned to accelerate the development of these glycan-based strategies. Through advanced chemical and enzymatic synthesis platforms, Asparia produces structurally defined glycans that are essential for constructing high-quality glycan microarrays and for mapping carbohydrate–antibody interactions with precision. Our expertise in glycan synthesis and microarray fabrication supports the systematic exploration of complex polysaccharide epitopes, facilitating the discovery of novel diagnostic biomarkers and vaccine candidates. By bridging the gap between synthetic glycan chemistry and translational immunology, Asparia Glycomics contributes to overcoming one of the major bottlenecks in antifungal research, the availability of well-defined carbohydrate structures for reliable and reproducible immune profiling.
References
(1) Zasłona, M. E.; Downey, A. M.; Seeberger, P. H.; Moscovitz, O. Semi- and Fully Synthetic Carbohydrate Vaccines against Pathogenic Bacteria: Recent Developments. Biochem. Soc. Trans. 2021, 49 (5), 2411–2429. https://doi.org/10.1042/BST20210766.
(2) Seeberger, P. H. Discovery of Semi- and Fully-Synthetic Carbohydrate Vaccines Against Bacterial Infections Using a Medicinal Chemistry Approach. Chem. Rev. 2021, 121 (7), 3598–3626. https://doi.org/10.1021/acs.chemrev.0c01210.
(3) Bays, D. J.; Jenkins, E. N.; Lyman, M.; Chiller, T.; Strong, N.; Ostrosky-Zeichner, L.; Hoenigl, M.; Pappas, P. G.; Iii, G. R. T. Epidemiology of Invasive Candidiasis. Clin. Epidemiol. 2024, 16, 549–566. https://doi.org/10.2147/CLEP.S459600.
(4) Fisher, M. C.; Denning, D. W. The WHO Fungal Priority Pathogens List as a Game-Changer. Nat. Rev. Microbiol. 2023, 21 (4), 211–212. https://doi.org/10.1038/s41579-023-00861-x.
(5) Reuber, E. E.; Hickey, E.; Pradhan, A.; Sprute, R.; Lingscheid, T.; Tober-Lau, P.; Leaves, I.; Stappers, M. H. T.; Kurth, F.; Bruno, M.; Netea, M. G.; Sander, L. E.; Cornely, O. A.; Gow, N. A. R.; Brown, A. J. P.; Singh, R. K.; Omoregbee-Leichnitz, S.; Sletten, E. T.; Danglad-Flores, J.; Seeberger, P. H. Glycan Microarray Analysis of Candida-Related Antibodies in Human and Mice Sera Guides Biomarker Discovery and Vaccine Development. Proc. Natl. Acad. Sci. 2025, 122 (39), e2505340122. https://doi.org/10.1073/pnas.2505340122.
(6) Gow, N. A. R.; Lenardon, M. D. Architecture of the Dynamic Fungal Cell Wall. Nat. Rev. Microbiol. 2023, 21 (4), 248–259. https://doi.org/10.1038/s41579-022-00796-9.