Immunotherapeutic Strategies for Fungal Infections

Invasive fungal infections remain a major global health threat, particularly among immunocompromised patients, with pathogens such as Candida, Aspergillus, Cryptococcus and emerging species like Candida auris causing high mortality despite available antifungal drugs. Limitations of conventional therapy—including drug toxicity, limited spectrum and rising resistance—have driven interest in immunotherapeutic alternatives that harness or modulate the host immune response. Broadly, these interventions fall into four categories: vaccines to elicit protective adaptive immunity; monoclonal antibodies for passive immunotherapy; cellular therapies that augment antifungal effector cells; and innate-immune modulators that prime long-lasting trained immunity. Vaccine approaches under investigation include subunit formulations targeting conserved cell-wall antigens, live-attenuated or inactivated whole-cell preparations and novel mRNA platforms formulated in lipid nanoparticles. Monoclonal antibodies directed against fungal surface epitopes such as β-glucan or adhesin proteins have shown efficacy in opsonisation and growth inhibition. Adoptive cell therapies, for example the transfer of antigen-specific T cells or natural killer cells, offer promise in profoundly immunosuppressed hosts. Finally, agents that engage pattern recognition receptors or induce epigenetic reprogramming of innate cells aim to boost early antifungal defences. Together, these strategies offer complementary routes to prevent and treat fungal diseases, with potential to reduce reliance on traditional antifungals and improve outcomes in high-risk populations.

Research from Nature Portfolio

Researchers have generated fully human monoclonal antibodies by isolating memory B cells from patients recovering from candidiasis and expressing recombinant antibodies against key Candida cell-wall proteins. These antibodies display high-avidity, morphology-specific binding to the fungal surface, promote efficient opsonophagocytosis by macrophages and confer protection in a murine model of disseminated candidiasis. This seminal work establishes a platform for clinical development of antibody therapies against invasive fungal infections.

Immunotherapeutic Strategies for Fungal Infections publication trend

The graph below shows the total number of articles in immunotherapeutic strategies for fungal infections across all publications each year (not limited to Nature Index journals).

Technical terms

Adaptive immunity: The arm of the immune system that generates pathogen-specific T and B lymphocyte responses, including memory formation.

Innate immunity: The first line of defence comprising non-specific cellular and molecular mechanisms, such as neutrophils, macrophages and pattern recognition receptors.

Monoclonal antibody: A homogeneous antibody population produced by a single B-cell clone, designed to bind a specific antigen with high affinity.

Lipid nanoparticle: A nanoscale vesicle composed of lipids, used to encapsulate and deliver nucleic acids or protein antigens in vaccine formulations.

Opsonophagocytosis: The process by which pathogens coated with opsonins (antibodies or complement) are recognised and ingested by phagocytic cells.

Th1/Th17 response: T helper cell subsets characterised by production of interferon-γ (Th1) or interleukin-17 (Th17), critical for host defence against intracellular and extracellular fungi, respectively.

References

1. Design of a lipid nano-delivery system containing recombinant Candida albicans chitinase 3 as a potential vaccine against fungal infections. Biomedicine & Pharmacotherapy (2023).
2. A chemically induced attenuated strain of Candida albicans generates robust protective immune responses and prevents systemic candidiasis development. eLife (2024).
3. Tailoring mRNA lipid nanoparticles for antifungal vaccines. PLOS Pathogens (2025).
4. Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis. Nature Communications (2018).
5. Protection by Anti-β-Glucan Antibodies Is Associated with Restricted β-1,3 Glucan Binding Specificity and Inhibition of Fungal Growth and Adherence. PLOS ONE (2009).