1. Novel mouse monoclonal antibodies specifically recognizing β-(1→3)-D-glucan antigen
- Author
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Yury E. Tsvetkov, D. V. Yashunsky, Ivan K. Baykov, Yana A. Khlusevich, Alexander A. Karelin, Vadim B. Krylov, Sarah Sze Wah Wong, Vishukumar Aimanianda, Jean-Paul Latgé, Alevtina V. Bardashova, Nina V. Tikunova, Nikolay E. Nifantiev, Andrey L. Matveev, Ljudmila A. Emelyanova, Institute of Chemical Biology and Fundamental Medicine [Novosibirsk, Russia] (ICBFM SB RAS), Siberian Branch of the Russian Academy of Sciences (SB RAS), ND Zelinsky Institute of Organic Chemistry [Moscow, Russia], Novosibirsk State University (NSU), Aspergillus, Institut Pasteur [Paris], Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Franco-German ANR-DFG (ANR-16-CE92-0031-01 AFUINTERACT to V. Kumar, (http://www.agence-nationale-recherche.fr) and the Franco-Indian CEFIPRA (Project N° 5403-1 to V. Kumar) grants., Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and ANR-16-CE92-0031,EpiFUS,Rôle de FUS dans la régulation des modifications épigénétiques : conséquences pour la sclérose latérale amyotrophique et la démence frontotemporale(2016)
- Subjects
0301 basic medicine ,Antifungal Agents ,beta-Glucans ,[SDV]Life Sciences [q-bio] ,MESH: Drug Synergism ,Aspergillus fumigatus ,MESH: Antibodies, Monoclonal ,Mice ,Cell Wall ,Candida albicans ,MESH: Animals ,Bovine serum albumin ,Fluconazole ,MESH: Treatment Outcome ,chemistry.chemical_classification ,MESH: Microbial Sensitivity Tests ,Multidisciplinary ,biology ,MESH: beta-Glucans ,Candidiasis ,Antibodies, Monoclonal ,Drug Synergism ,Oligosaccharide ,MESH: Candidiasis ,3. Good health ,Treatment Outcome ,Biochemistry ,Biotinylation ,Medicine ,MESH: Fluconazole ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Drug Therapy, Combination ,Female ,MESH: Aspergillus fumigatus ,Research Article ,Antigens, Fungal ,medicine.drug_class ,Science ,030106 microbiology ,Microbial Sensitivity Tests ,Monoclonal antibody ,03 medical and health sciences ,MESH: Cell Wall ,medicine ,Animals ,Humans ,MESH: Mice ,MESH: Antigens, Fungal ,MESH: Humans ,MESH: Candida albicans ,[SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy ,biology.organism_classification ,MESH: Antifungal Agents ,In vitro ,Disease Models, Animal ,MESH: Drug Therapy, Combination ,030104 developmental biology ,chemistry ,biology.protein ,Hybridoma technology ,MESH: Disease Models, Animal ,MESH: Female - Abstract
International audience; 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.
- Published
- 2019