Development of an Immunochromatographic Lateral-Flow Device for Rapid Serodiagnosis of Invasive Aspergillosis
Open accessAbstract
Aspergillus fumigatus is a cosmopolitan saprotrophic fungus that is second only to Candida species as a cause of invasive fungal infections in immunocompromised humans. Current immunodiagnostic tests for invasive aspergillosis (IA) are based on the detection of circulating galactomannan (GM) in a patient's serum by using a rat monoclonal antibody (MAb), EB-A2, that binds to tetra (1→5)-β- d -galactofuranoside, the immunodominant epitope in GM. The potential cross-reactivity of MAb EB-A2 with non- Aspergillus fungi, with contaminating GM in β-lactam antibiotics and foodstuffs, and with bacterial lipoteichoic acids has prompted efforts to discover non-GM antigens that can act as surrogate markers for the diagnosis of IA. This paper describes the development of a mouse MAb, JF5, that binds to a protein epitope present on an extracellular glycoprotein antigen secreted constitutively during the active growth of A. fumigatus . The MAb was used to develop an immunochromatographic lateral-flow device (LFD) for the rapid (15-min) detection of Aspergillus antigens in human serum. The test is highly specific, reacting with antigens from Aspergillus species but not with antigens from a large number of clinically important fungi, including Candida species, Cryptococcus neoformans , Fusarium solani , Penicillium marneffei , Pseudallescheria boydii , and Rhizopus oryzae . The LFD was able to detect circulating antigen in serum samples from patients suspected of having or shown to have IA on the basis of their clinical symptoms and results from tests for GM and fungal (1→3)-β- d -glucan. The ease of use of the LFD provides a diagnostic platform for the routine testing of vulnerable patients who have an elevated risk of IA.
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A MAb recognizing a galactofuranose-rich peptidoglycan molecule that circulates in serum and other biological fluids of patients with IA has been selected.
“Another MAb recognizing a galactofuranose-rich peptidoglycan molecule that circulates in serum and other biological fluids of patients with IA has been selected (124, 125).”
From Aspergillus fumigatus and Aspergillosis in 2019 (2019) · cites this paper as [124]
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Piarroux, R., Romain, T., Martin, A., Vainqueur, D., Vitte, J., Lachaud, L., Gangneux, J., Gabriel, F., Fillaux, J., & Ranque, S. (2019) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2019.00012 · Cited by 51 · see citing works
Thornton, C. R., Johnson, G. L., & Agrawal, S. G. (2012) · Journal of Visualized Experiments · doi:10.3791/3721 · Cited by 52 · see citing works
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Molecular Imaging of Invasive Pulmonary Aspergillosis Using ImmunoPET/MRI: The Future Looks Bright
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Self-citationWiederhold, N. P., Thornton, C. R., Najvar, L. K., Kirkpatrick, W. R., Bocanegra, R. A., & Patterson, T. F. (2009) · Clinical and Vaccine Immunology · doi:10.1128/cvi.00268-09 · Cited by 48 · see citing works
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Thornton, C. R., & Wills, O. E. (2013) · Critical Reviews in Microbiology · doi:10.3109/1040841x.2013.788995 · Cited by 46 · see citing works
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Bidula, S. M., Sexton, D. W., Abdolrasouli, A., Shah, A., Reed, A. K., Armstrong-James, D. P. H., & Schelenz, S. (2015) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiv027 · Cited by 44 · see citing works
Nonmolecular Methods for the Diagnosis of Respiratory Fungal Infections
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Molecular Imaging: a Novel Tool To Visualize Pathogenesis of Infections In Situ
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Invasive pulmonary aspergillosis: current diagnostic methodologies and a new molecular approach
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Outbreaks of Fungal Infections in Hospitals: Epidemiology, Detection, and Management
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Non-cultural methods for the diagnosis of invasive fungal disease
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Vaccines against candidiasis: Status, challenges and emerging opportunity
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Evaluation of a Novel Aspergillus Antigen Enzyme-Linked Immunosorbent Assay
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Thornton, C. (2009) · Clinical and Vaccine Immunology · doi:10.1128/cvi.00061-09 · Cited by 44 · see citing works
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Zhang, L., Guo, Z., Xie, S., Zhou, J., Chen, G., Feng, J., & Huang, Y. (2019) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2018.08.005 · Cited by 36 · see citing works
New pathogen-specific immunoPET/MR tracer for molecular imaging of a systemic bacterial infection
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Kovanda, L. L., Desai, A. V., & Hope, W. W. (2017) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1007/s10928-017-9509-1 · Cited by 30 · see citing works
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Yu, L., Rodríguez-Manzano, J., Moser, N., Moniri, A., Malpartida-Cardenas, K., Miscourides, N., Sewell, T. R., Kochin, D., Brackin, A. P., Rhodes, J. L., et al. (2020) · Journal of Clinical Microbiology · doi:10.1128/jcm.00843-20 · Cited by 30 · see citing works
Mercier, T., Schauwvlieghe, A. F. A. D., de Kort, E., Dunbar, A., Reynders, M., Guldentops, E., Rijnders, B. J. A., Verweij, P. E., Lagrou, K., & Maertens, J. A. (2019) · Journal of Clinical Microbiology · doi:10.1128/jcm.01913-18 · Cited by 30 · see citing works
Miceli, M. H., Goggins, M. I., Chander, P., Sekaran, A. K., Kizy, A. E., Samuel, L., Jiang, H., Thornton, C. R., Ramesh, M., & Alangaden, G. (2015) · Mycoses · doi:10.1111/myc.12327 · Cited by 30 · see citing works
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Monoclonal Antibodies and Invasive Aspergillosis: Diagnostic and Therapeutic Perspectives
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Recent Advances and Novel Approaches in Laboratory-Based Diagnostic Mycology
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Current and Future Pathways in Aspergillus Diagnosis
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Laboratory Diagnostics for Fungal Infections
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Point-of-care testing for viral-associated pulmonary aspergillosis
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Self-citationTwo cases of severe pneumonia after the 2011 Great East Japan Earthquake
Nakadate, T., Nakamura, Y., Yamauchii, K., & Endo, S. (2012) · Western Pacific surveillance response journal · doi:10.5365/wpsar.2012.3.2.002 · Cited by 21 · see citing works
Sérologie aspergillaire, d’hier à aujourd’hui pour demain
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- Authors
- Thornton, C. R.
- Affiliations
- University of Exeter (GB)
- Corresponding author
- Thornton, Christopher R.
- Venue
- Clinical and Vaccine Immunology
- Publisher
- American Society for Microbiology
- Published
- 2008-07
- Volume
- 15
- Issue
- 7
- Pages
- 1095-1105
- ISSN
- 1556-679X (ISSN-L)
- 1556-6811
- PMC
- PMC2446636
- OpenAlex
- W2131814154
- Cited by
- 226
- References
- 49
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 9 · 2023: 21 · 2022: 14 · 2021: 13 · 2020: 14 · 2019: 20 · 2018: 21 · 2017: 16 · 2016: 20 · 2015: 22 · 2014: 14 · 2013: 11 · 2012: 6
- FWCI
- 1.55
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Clinical and Vaccine Immunology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Biosensors and Analytical Detection
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Keywords
- invasive aspergillosis, Aspergillus fumigatus, serological diagnosis, rapid antigen detection, immunocompromised patients, galactomannan, β-glucan, diagnostic specificity
- MeSH terms
- Antibodies, Fungal, Antibodies, Monoclonal, Antibody Specificity, Epitopes, Antigens, Fungal, Aspergillosis, Aspergillus fumigatus, Cross Reactions, Humans, Periodic Acid, Pronase, Sensitivity and Specificity, Serologic Tests, Trypsin, Microscopy, Immunoelectron
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