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Published on: March 22, 2012
A Novel Monoclonal Antibody 1D2 That Broadly Inhibits Clinically Important Aspergillus Species
Xihua Lian1,2, Amy Scott-Thomas1, John G Lewis1,3
1Department of Pathology and Biomedical Science, University of Otago, Christchurch 8140, New Zealand.
Abstract:
Aspergillus fumigatus is a ubiquitous airborne fungus, is the predominant cause (>90%) of invasive aspergillosis (IA) in immunosuppressed patients and has a high mortality. New approaches to prevention and treatment are needed because of the poor efficacy, toxicity and side effects of the current anti-Aspergillus drugs on patients. Thus, we aim to explore a new avenue to combat Aspergillus infection by using a novel monoclonal antibody (mAb) 1D2 against a glycoprotein on the cell wall of Aspergillus. The ability of this mAb to inhibit attachment, germination, and growth of Aspergillus conidia and hyphae in vitro were examined. A dose-dependent growth inhibition of Aspergillus conidia in the presence of mAb 1D2 was found. The mAb 1D2 inhibited attachment of Aspergillus conidia to an untreated slide surface and fibronectin-treated surface compared to an unrelated mAb 6B10. When conidia were exposed to 1D2 concomitantly with inoculation into culture media, the mAb prevented the swelling and germination of conidia. This inhibitory ability of 1D2 was less apparent if it was added two hours after inoculation. Damage to hyphae was also observed when 1D2 was added to Aspergillus hyphae that had been incubated in media overnight. These in vitro results indicate that mAb 1D2 broadly inhibits clinically important Aspergillus species and has a promising therapeutic effect both as prophylaxis to inhibit an Aspergillus infection as well as a treatment.
Insights
A novel monoclonal antibody, mAb 1D2, effectively inhibits Aspergillus fumigatus, a fungus causing invasive aspergillosis in immunocompromised patients. This antibody shows promise for preventing and treating fungal infections.
Area of Science:
- Mycology
- Immunology
- Infectious Diseases
Background:
- Aspergillus fumigatus is a major cause of invasive aspergillosis (IA) in immunosuppressed individuals.
- Current antifungal treatments have limitations including poor efficacy and toxicity.
- Novel therapeutic strategies are crucial for managing IA.
Purpose of the Study:
- To investigate the potential of a novel monoclonal antibody (mAb) 1D2 targeting Aspergillus cell wall glycoproteins.
- To evaluate the in vitro efficacy of mAb 1D2 in inhibiting Aspergillus conidia and hyphae.
Main Methods:
- In vitro assessment of mAb 1D2's effect on Aspergillus conidia attachment, germination, and growth.
- Comparison of mAb 1D2 with an unrelated antibody (mAb 6B10).
- Evaluation of mAb 1D2's impact on established Aspergillus hyphae.
Main Results:
- mAb 1D2 demonstrated dose-dependent inhibition of Aspergillus conidia growth.
- mAb 1D2 significantly inhibited conidia attachment to surfaces.
- Concomitant exposure to mAb 1D2 prevented conidia germination; delayed addition showed reduced efficacy.
- Damage to Aspergillus hyphae was observed with mAb 1D2 treatment.
Conclusions:
- mAb 1D2 exhibits broad inhibitory activity against clinically relevant Aspergillus species in vitro.
- mAb 1D2 shows potential as a therapeutic agent for both prophylaxis and treatment of Aspergillus infections.

