Monoclonal antibodies targeting Candida cell wall and cell-surface antigens: a systematic review

Invasive candidiasis remains associated with high mortality, while multidrug-resistant species such as Candida auris have increased interest in antibody-based immunotherapies.

To systematically evaluate monoclonal antibodies (mAbs) targeting Candida cell wall proteins (CWPs), their mechanisms of protection, and translational challenges.

PubMed, Scopus, Web of Science, and Embase were searched (2003-2025) following PRISMA 2020 guidelines. Studies reporting characterised mAbs against defined CWP targets with protective data were included.

Twelve studies met the inclusion criteria. Ten target categories were identified, including Hwp1, Hyr1, Hsp90, Utr2/Pga31, Ssa1, and β-1,2-mannoside/mannotriose glycotopes. Protective mechanisms included opsonophagocytosis, biofilm inhibition, immune modulation, and direct disruption of fungal integrity. Cross-species activity against C. auris was reported for several antibodies. Mycograb (anti-Hsp90) is the only passive mAb identified to have reached advanced (Phase III) clinical evaluation; Als3 has reached Phase 2 evaluation via the NDV-3A active-vaccination platform rather than passive mAb therapy.

Candida CWPs represent promising antibody targets, but clinical translation requires antibody humanisation, pharmacokinetic studies, and well-designed combination trials.