Novel Monoclonal Antibodies 1D2 and 4E4 Against Aspergillus Glycoprotein Antigens Detect Early Invasive Aspergillosis in Mice

被引：0
作者：
Lian, Xihua [1 ,2 ]
Scott-Thomas, Amy [1 ]
Lewis, John G. [1 ]
Bhatia, Madhav [1 ]
Chambers, Stephen T. [1 ]
机构：
[1] Univ Otago, Dept Pathol & Biomed Sci, Christchurch 8140, New Zealand
[2] Fujian Med Univ, Clin Med Sch 2, Dept Ultrasound Med, Quanzhou 362000, Peoples R China
来源：
JOURNAL OF FUNGI | 2024年 / 10卷 / 12期
关键词：
monoclonal antibody; <italic>Aspergillus</italic>; invasive aspergillosis; mice; FUMIGATUS; INFECTION; DIAGNOSIS; CAPTURE;
D O I：
10.3390/jof10120832
中图分类号：
Q93 [微生物学];
学科分类号：
071005 ; 100705 ;
摘要：
Due to the high morbidity and mortality rates of invasive aspergillosis (IA) and the importance of early IA detection for successful treatment and subsequent outcome, this study aimed to determine a time course of detectable antigen in a mouse model of IA and correlate it with tissue invasion by using two novel monoclonal antibodies, 1D2 and 4E4, that can be used to detect the Aspergillus-derived glycoproteins. Immunocompromised mice were randomly divided into five groups: uninfected control, and inoculation with conidia from Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, and Aspergillus terreus. Conidia (2 x 106 cells/mL) were administered intravenously via tail vein injection. Three mice from each group were euthanised at each time point (6 h, 12 h, 18 h, 24 h, and 48 h) after inoculation. Urine and blood were collected for analysis using a double-sandwich ELISA using 1D2 and 4E4. Liver, spleen, and kidney tissues were harvested for tissue staining. The levels of liver injury in the IA mice progressively increased with time after inoculation with Aspergillus conidia. Following inoculation with A. fumigatus, swollen conidia were identified in the spleen, as well as antigens in blood after 18 h. Hyphae were detected in the spleen, liver, and kidney after 48 h. For A. flavus, the antibodies detected hyphae in the liver and spleen as well as circulating antigens in blood samples 48 h after inoculation. Tissue injury was observed in the mice inoculated with A. terreus and A. niger, but there was no evidence of fungal invasion or antigens in the blood. Antigens were not detectable in mouse urine but could be detected in glomeruli of the kidney by immunofluorescence. In conclusion, the mAb-based antigen detection double-sandwich ELISA results were consistent with the IHC results in this study. Novel monoclonal antibodies 1D2 and 4E4 can serve as tools for the early identification of IA in mice infected by A. fumigatus and A. flavus. This study also suggests the potential usefulness of this approach in human disease.
引用
收藏
页数：13
相关论文
共 29 条
  • [1] Girmenia C., Raiola A.M., Piciocchi A., Algarotti A., Stanzani M., Cudillo L., Pecoraro C., Guidi S., Iori A.P., Montante B., Et al., Incidence and Outcome of Invasive Fungal Diseases after Allogeneic Stem Cell Transplantation: A Prospective Study of the Gruppo Italian Trapianto Midollo Osseo (GITMO), Biol. Blood Marrow Transplant, 20, pp. 872-880, (2014)
  • [2] Lass-Florl C., How to make a fast diagnosis in invasive aspergillosis, Med. Mycol, 57, pp. S155-S160, (2019)
  • [3] Donnelly J.P., Chen S.C., Kauffman C.A., Steinbach W.J., Baddley J.W., Verweij P.E., Clancy C.J., Wingard J.R., Lockhart S.R., Groll A.H., Et al., Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium, Clin. Infect. Dis, 71, pp. 1367-1376, (2020)
  • [4] Cadena J., Thompson G.R., Patterson T.F., Aspergillosis Epidemiology, Diagnosis, and Treatment, Infect. Dis. Clin. N. Am, 35, pp. 415-434, (2021)
  • [5] Blaize M., Mayaux J., Nabet C., Lampros A., Marcelin A.G., Thellier M., Piarroux R., Demoule A., Fekkar A., Fatal Invasive Aspergillosis and Coronavirus Disease in an Immunocompetent Patient, Emerg. Infect. Dis, 26, pp. 1636-1637, (2020)
  • [6] Schauwvlieghe A.F.A.D., Rijnders B.J.A., Philips N., Verwijs R., Vanderbeke L., Van Tienen C., Lagrou K., Verweij P.E., Van de Veerdonk F.L., Gommers D., Et al., Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: A retrospective cohort study, Lancet Respir. Med, 6, pp. 782-792, (2018)
  • [7] Ullmann A.J., Aguado J.M., Arikan-Akdagli S., Denning D.W., Groll A.H., Lagrou K., Lass-Florl C., Lewis R.E., Munoz P., Verweij P.E., Et al., Diagnosis and management of Aspergillus diseases: Executive summary of the 2017 ESCMID-ECMM-ERS guideline, Clin. Microbiol. Infect, 24, pp. e1-e38, (2018)
  • [8] Lian X., Scott-Thomas A., Lewis J.G., Bhatia M., MacPherson S.A., Zeng Y., Chambers S.T., Monoclonal Antibodies and Invasive Aspergillosis: Diagnostic and Therapeutic Perspectives, Int. J. Mol. Sci, 23, (2022)
  • [9] Gunzer M., Thornton C.R., Beziere N., Advances in the In Vivo Molecular Imaging of Invasive Aspergillosis, J. Fungi, 6, (2020)
  • [10] Marr K.A., Datta K., Mehta S., Ostrander D.B., Rock M., Francis J., Feldmesser M., Urine Antigen Detection as an Aid to Diagnose Invasive Aspergillosis, Clin. Infect. Dis, 67, pp. 1705-1711, (2018)
123