title: Humoral and cell-mediated immunity following vaccination with synthetic Candida cell wall mannan derived heptamannoside-protein conjugate: immunomodulatory properties of heptamannoside-BSA conjugate.
abstract: Chemically defined glycoprotein conjugate composed of synthetically prepared mannan-derived heptamannoside with terminal β-1,2-linked mannose residue attached to the α-1,3-linked mannose residues and BSA as carrier protein (M7-BSA conjugate) was analysed for the capacity to induce protective humoral immunity and appropriate alteration cellular immunity. To identify protective antigenic structure of Candida cell wall mannan M7-BSA conjugate was used for BALB/c mice immunization. The obtained results were compared with placebo group and with heat-inactivated C. albicans whole cells immunization. The administration route of M7-BSA conjugate secondary booster injection significantly affected the intensity of humoral immune response and the specificity of produced antibodies. All prepared sera were able to elevate candidacidal activity of polymorphonuclear leukocytes (PMN) in cooperation with complement. Moreover, polyclonal sera obtained after secondary subcutaneous (s.c.) booster injection of M7-BSA conjugate were able to induce candidacidal activity of PMN also in complement independent manner. M7-BSA conjugate immunization induced increases of phagocytic activity and respiratory burst of granulocytes, caused a raise of the proportion of CD3(+) T lymphocytes and increased the CD4(+)/CD8(+) T lymphocyte ratio. We observed also an increasing proportion of CD4(+)CD25(+) T cells compared to immunization with heat inactivated whole C. albicans cells, which in turn promoted an increase of the CD8(+)CD25(+) cell proportion. Immunization with M7-BSA conjugate induced Th1, Th2 and Th17 immune responses as indicated by the elevation of relevant cytokines levels. These data provide some insights on the immunomodulatory properties of oligomannosides and contribute to the development of synthetic oligosaccharide vaccines against fungal diseases.
authors: Institute of Chemistry, Centre of excellence Glycomed, Department of Immunochemistry of Glycoconjugates, Slovak Academy of Sciences, Bratislava, Slovakia. chemluli@savba.sk
authors: Lucia
authors: L
authors: Paulovičová
authors: Ema
authors: E
authors: Paulovičová
authors: Alexander A
authors: AA
authors: Karelin
authors: Yury E
authors: YE
authors: Tsvetkov
authors: Nikolay E
authors: NE
authors: Nifantiev
authors: Slavomír
authors: S
authors: Bystrický
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D002177:Candidiasis / Q000276:immunology*; D002473:Cell Wall / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D005260:Female; D005657:Fungal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D056747:Immunomodulation; D008351:Mannans / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000908:Antibodies, Fungal; D015703:Antigens, CD; D016207:Cytokines; D000939:Epitopes; D005657:Fungal Vaccines; D008351:Mannans; D018074:Vaccines, Conjugate; D012710:Serum Albumin, Bovine