A Murine, Bispecific Monoclonal Antibody Simultaneously Recognizing β-Glucan and MP65 Determinants in Candida Species

PLoS One. 2016 Feb 9;11(2):e0148714. doi: 10.1371/journal.pone.0148714. eCollection 2016.

Abstract

There is a real medical need of new diagnostic tools for the early recognition of invasive Candida infections. We exploited a rather simple and rapid redox methodology to construct a bispecific monoclonal antibody (bsmAb) that combines a monoclonal antibody (mAb) directed against 1,3-β-D-glucan, a well-known, pan-fungal diagnostic biomarker, with a mAb recognizing MP65, a major immunogenic mannoprotein secreted by C.albicans and other Candida species. The bsmAb (MP65/bglu mAb) was successfully produced and purified at high yields and proved to bind and reveal simultaneously, with high sensitivity, the β-glucan and MP65 antigens in both purified and native forms. The MP65/bglu mAb is the first bispecific antibody generated against a fungal microorganism and may prove useful for the concurrent detection of different and clinically significant Candida biomarkers in patient sera.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Animals
  • Antibodies, Bispecific / immunology*
  • Antibodies, Fungal / immunology
  • Antibodies, Monoclonal / immunology
  • Antibody Specificity
  • Antigens, Fungal / blood
  • Antigens, Fungal / immunology*
  • Biomarkers / blood
  • Candida / immunology*
  • Candida albicans / immunology
  • Candidiasis, Invasive / blood
  • Candidiasis, Invasive / diagnosis
  • Candidiasis, Invasive / immunology
  • Fungal Proteins / blood
  • Fungal Proteins / immunology
  • Humans
  • Immunodominant Epitopes / blood
  • Immunodominant Epitopes / immunology
  • Membrane Glycoproteins / blood
  • Membrane Glycoproteins / immunology
  • Mice
  • Serologic Tests
  • beta-Glucans / immunology*

Substances

  • Antibodies, Bispecific
  • Antibodies, Fungal
  • Antibodies, Monoclonal
  • Antigens, Fungal
  • Biomarkers
  • Fungal Proteins
  • Immunodominant Epitopes
  • Membrane Glycoproteins
  • beta-Glucans
  • mannoproteins

Grants and funding

The work in Torino was supported by the Fondo per gli investimenti della ricerca di base (FIRB, Rome, Italy), Fondazione Ricerca Molinette and Fondazione CRT (both in Torino, Italy) to FM. Work in Rome was granted by the Gilead Fellowship Program 2012 to RC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.