Monoclonal antibodies to hyphal exoantigens derived from the opportunistic pathogen, Aspergillus terreus

Details

• Personal Author:
  Beezhold, Donald H. ; Friend S ; Green, Brett J. ; Hettick JM ; Janotka E ; Nayak, Ajay P. ; Schmechel D ; Vesper SJ
• Description:
  A. terreus has been difficult to identify in cases of aspergillosis and clinical identification has been restricted to the broad identification of aspergillosis lesions in affected organs or the detection of fungal carbohydrates. As a result, there is a clinical need to identify species-specific biomarkers that can be used to detect invasive A. terreus disease. Monoclonal antibodies (mAbs) were developed to a partially purified preparation of cytolytic hyphal exoantigens (HEA) derived from A. terreus culture supernatant (CSN). Twenty-three IgG1 isotype murine mAbs were developed and tested for cross reactivity against hyphal extracts of 54 fungal species. Sixteen mAbs were shown to be specific for A. terreus. HEA antigens were detected in conidia, hyphae and in CSN of A. terreus. HEA antigens were expressed in high levels in the hyphae during early stages of A. terreus growth at 37 degrees C, whereas at room temperature, the expression of HEA antigens peaked by day 4-5. Expression kinetics of HEA antigens in CSN showed a lag, with peak levels at later time points at RT and 37 degrees C compared to hyphal extracts. Serum spiking experiments demonstrated that human serum components do not inhibit detection of the HEA antigen epitopes by mAb ELISA. Immunoprecipitation and proteomic analysis demonstrated that mAbs 13E11 and 12C4 immunoprecipitated a putative uncharacterized leucine aminopeptidase (Q0CAZ7), while mAb 19B2 recognized a putative dipeptidyl-peptidase V (DPP5). Studies using Confocal laser scanning microscopy showed that the uncharacterized leucine aminopeptidase mostly localized to extracellular matrix structures, while dipeptidyl-peptidase V was mostly confined to the cytoplasm. [Description provided by NIOSH]
• Subjects:
  Antibodies Antigens Biomarkers Cytology Fungi Growth Immune System Laboratories Microbiology Occupational Health Safety Temperature

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• Keywords:
  Antibody-response Author Keywords: Aspergillus Terreus Cell-biology Exoantigen Fungal-infections Growth-factors Growth-rate Humans Immune-reaction Immunoglobulin G Immunology Laboratory-techniques Laboratory-testing Monoclonal Antibody Statistical-analysis Temperature-effects Temperature-measurement

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• ISSN:
  1556-6811
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Georgia ; Ohio ; OSHA Region 4 ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  18
• Issue:
  9
• NIOSHTIC Number:
  nn:20039092
• Citation:
  Clin Vaccin Immunol 2011 Sep; 18(9):1568-1576
• Contact Point Address:
  Donald H. Beezhold, Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV
• Federal Fiscal Year:
  2011
• NORA Priority Area:
  Healthcare and Social Assistance ; Services
• Peer Reviewed:
  True
• Source Full Name:
  Clinical and Vaccine Immunology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ab93f1f7da42612ff5f21aece57616e6eaed05e5c355e1f946613fe1e4bcd7a7775a43fc71b9ace952dfaf8081e66a230f122b2242094e53cf648e0f6e06c651
• Download URL:
  https://stacks.cdc.gov/view/cdc/192574/cdc_192574_DS1.pdf
• File Type:
  [PDF - 1.02 MB ]