The evaluation of β-(1 → 3)-nonaglucoside as an anti-Candida albicansimmune response inducer

Abstract

Synthetically prepared bovine serum albumin (BSA) conjugate of linear β-(1 → 3)-nonaglucoside ligand (G9) has been applied as a biological response immunomodulator in vivo and ex vivo. Active immunization of Balb/c mice revealed effective induction of specific humoral responses in comparison with Candida β-D-glucan and Candida whole cells. Induced post-vaccination serum exhibited a growth-inhibition effect on the multi-azole-resistant clinical strain Candida albicans CCY 29-3-164 in experimental mucocutaneous infection ex vivo. Evaluation of immune cell proliferation and the cytotoxic potential of the G9-ligand has revealed its bioavailability and an immunostimulative effect in vaccination-sensitized Balb/c mice splenocytes and RAW 264.7 macrophages.

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

“…To generate mAbs specifically recognizing fungal β-(1→3)-D-glucan, the synthetic β-(1→3)-linked nonaglucoside G9 was selected as target ligand. The conjugates of this oligosaccharide demonstrated high immunogenicity [14]. Moreover, theoretical and experimental conformational studies showed that the nonasaccharide sequence is long enough to mimic natural β-(1→3)-linked glucan [31].…”

“…The synthesis of spacer-armed oligosaccharides related to β-(1→3)-D-glucan fragments has been described previously [15–17]. Bovine serum albumin (BSA) conjugate of nona-β-(1→3)-D-glucoside ( G9-BSA ) was prepared from parent aminopropyl glycoside ( G9 ) using the squarate protocol [14] (Fig 1). According to MALDI TOF MS data, G9-BSA contained on average ~10 oligosaccharide chains per protein molecule.…”

“…In this study, we describe selection and characterization of two anti-β-(1→3)-D-glucan monoclonal antibodies (5H5 and 3G11) that were developed with the use of nona-β-(1→3)-D-glucoside-BSA conjugate [14] G9-BSA (Fig 1). The nonaglucoside ligand in this preparation represents the linear fragments of β-(1→3)-D-glucan.…”

Importance of Candida Antigenic Factors: Structure-Driven Immunomodulation Properties of Synthetically Prepared Mannooligosaccharides in RAW264.7 Macrophages

“…Next, a novel tetrasaccharide construct consisting of β-1,2-mannopyranosyl trisaccharide and α-mannopyranoside was designed and suggested as a model of the C. albicans phosphodiester epitope (Dang et al, 2012). Glycoarrays formed by biotinylated oligosaccharides loaded on streptavidin-coated surfaces were previously shown to be indispensable instruments for the investigation of carbohydrate antigen recognition by immune cells (Komarova et al, 2015, 2018; Akhmatova et al, 2016; Paulovicova et al, 2016, 2017; Kurbatova et al, 2017; Argunov et al, 2019; Schubert et al, 2019).…”

“…Moreover, the sera reactivity and determination of antigen-specific isotypic antibodies against synthetically prepared mannooligosaccharides were evaluated in a cohort of patients with vulvovaginal candidosis (Karelin et al, 2016; Paulovicova et al, 2016, 2017). Postvaccination antisynthetic heptamannoside polyclonal sera inhibited growth of the azole-resistant clinical strain C. albicans CCY 29-3-164 and reduced the number of colony-forming units throughout an experimental mucosal infection (Paulovicova E. et al, 2013).…”