Journal Article

Novel mouse monoclonal antibodies specifically recognizing β-(1→3)-D-glucan antigen

Tikunova, Nina V., Karelin, Alexander A., Emelyanova, Ljudmila A., Tsvetkov, Yury E., Wong, Sarah S. W., Yashunsky, Dmitry V., Nifantiev, Nikolay E., Krylov, Vadim B., Bardashova, Alevtina V., Matveev, Andrey L., Aimanianda, Vishukumar, Baykov, Ivan K., Latgé, Jean-Paul, Khlusevich, Yana A.

2019

Overview

β-(1→3)-D-Glucan is an essential component of the fungal cell wall. Mouse monoclonal antibodies (mAbs) against synthetic nona-β-(1→3)-D-glucoside conjugated with bovine serum albumin (BSA) were generated using hybridoma technology. The affinity constants of two selected mAbs, 3G11 and 5H5, measured by a surface plasmon resonance biosensor assay using biotinylated nona-β-(1→3)-D-glucan as the ligand, were approximately 11 nM and 1.9 nM, respectively. The glycoarray, which included a series of synthetic oligosaccharide derivatives representing β-glucans with different lengths of oligo-β-(1→3)-D-glucoside chains, demonstrated that linear tri-, penta- and nonaglucoside, as well as a β-(1→6)-branched octasaccharide, were recognized by mAb 5H5. By contrast, only linear oligo-β-(1→3)-D-glucoside chains that were not shorter than pentaglucosides (but not the branched octaglucoside) were ligands for mAb 3G11. Immunolabelling indicated that 3G11 and 5H5 interact with both yeasts and filamentous fungi, including species from Aspergillus, Candida, Penicillium genera and Saccharomyces cerevisiae, but not bacteria. Both mAbs could inhibit the germination of Aspergillus fumigatus conidia during the initial hours and demonstrated synergy with the antifungal fluconazole in killing C. albicans in vitro. In addition, mAbs 3G11 and 5H5 demonstrated protective activity in in vivo experiments, suggesting that these β-glucan-specific mAbs could be useful in combinatorial antifungal therapy.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Antibodies, Monoclonal / Antibodies, Monoclonal - immunology / Antibodies, Monoclonal - pharmacology / Antifungal Agents / Antifungal Agents - immunology / Antifungal Agents - pharmacology / Antigens, Fungal / Antigens, Fungal - immunology / Aspergillus fumigatus / Aspergillus fumigatus - drug effects / Aspergillus fumigatus - immunology / beta-Glucans / beta-Glucans - immunology / Biology / Biosensors / Bovine serum albumin / Candida albicans / Candida albicans - drug effects / Candida albicans - immunology / Candidiasis / Candidiasis - drug therapy / Candidiasis - immunology / Candidiasis - microbiology / Carbohydrates / Cell Wall / Cell Wall - drug effects / Cell Wall - immunology / Cell walls / Chain branching / Chains / Combinatorial analysis / Conidia / Disease Models, Animal / Drug Synergism / Drug Therapy, Combination / Female / Fluconazole / Fluconazole - pharmacology / Fungal infections / Fungi / Fungicides / Germination / Glucan / Glucans / Humans / Immunoglobulins / Immunology / Immunotherapy / Life Sciences / Ligands / Medicine / Mice / Microbial Sensitivity Tests / Monoclonal antibodies / Oligosaccharides / Organic chemistry / Saccharomyces cerevisiae / Serum albumin / Surface plasmon resonance / Treatment Outcome / Yeast / Yeasts / β-Glucan