Time-resolved fluoroimmunoassay for Aspergillus detection based on anti-galactomannan monoclonal antibody from stable cell line

Anal Biochem. 2024 Jun:689:115494. doi: 10.1016/j.ab.2024.115494. Epub 2024 Feb 23.

Abstract

Invasive Aspergillosis is a high-risk illness with a high death rate in immunocompromised people due to a lack of early detection and timely treatment. Based on immunology study, we achieved an efficient production of anti-galactomannan antibody by Chinese hamster ovary (CHO) cells and applied it to time-resolved fluoroimmunoassay for Aspergillus galactomannan detection. We first introduced dual promoter expression vector into CHO host cells, and then applied a two-step screening strategy to screen the stable cell line by methionine sulfoximine pressurization. After amplification and fermentation, antibody yield reached 4500 mg/L. Then we conjugated the antibodies with fluorescent microspheres to establish a double antibody sandwich time-resolved fluoroimmunoassay, which was compared with the commercial Platelia™ Aspergillus Ag by clinical serum samples. The preformed assay could obtain the results in less than 25 min, with a limit of detection for galactomannan of approximately 1 ng/mL. Clinical results of the two methods showed that the overall percent agreement was 97.7% (95% CI: 96.6%-98.4%) and Cohen's kappa coefficient was 0.94. Overall, the assay is highly consistent with commercial detection, providing a more sensitive and effective method for the rapid diagnosis of invasive aspergillosis.

Keywords: Anti-galactomannan antibody; Chinese hamster ovary cell; Glutamine synthetase screening; Stable cell line; Time-resolved fluoroimmunoassay.

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Aspergillosis* / diagnosis
  • Aspergillus*
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Fluoroimmunoassay
  • Galactose / analogs & derivatives*
  • Humans
  • Mannans

Substances

  • galactomannan
  • Mannans
  • Galactose
  • Antibodies, Monoclonal