Synthesis and immunological studies of glycoconjugates of Cryptococcus neoformans capsular glucuronoxylomannan oligosaccharide structures.
Antibodies to the glucuronoxylomannan (GXM) component of the polysaccharide capsule of Cryptococcus neoformans are protective and GXM-protein conjugate vaccines can elicit protective immune responses. We report the synthesis of a heptasaccharide oligosaccharide representing the putative dominant motif of serotype A GXM and demonstrate that it is recognized by some monoclonal antibodies (mAbs) generated to GXM. Conjugation of the heptasaccharide to human serum albumin (HSA) resulted in an immunogenic compound that elicited high-titer IgG responses in mice when given with complete Freund's adjuvant. The antibody response elicited by the oligosaccharide conjugate vaccine had characteristics of a T-cell-dependent response. The availability of an immunogenic oligosaccharide representing a structural motif of GXM will prove useful in studies of antibody epitope specificity and represents a potential synthetic oligosaccharide vaccine against this fungal pathogen.
Oscarson
Stefan
S
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, S-106 91 Stockholm, Sweden.
Alpe
Mia
M
Svahnberg
Pär
P
Nakouzi
Antonio
A
Casadevall
Arturo
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D000946:Antigens, Fungal / Q000737:chemistry* / Q000276:immunology*; D001710:Biotin; D002240:Carbohydrate Sequence; D002855:Chromatography, Thin Layer; D003455:Cryptococcus neoformans / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D005657:Fungal Vaccines / Q000138:chemical synthesis* / Q000276:immunology*; D006801:Humans; D007115:Immunization Schedule; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000138:chemical synthesis* / Q000276:immunology*; D012709:Serum Albumin / Q000737:chemistry
D000911:Antibodies, Monoclonal; D000946:Antigens, Fungal; D005657:Fungal Vaccines; D007202:Indicators and Reagents; D011134:Polysaccharides; D012709:Serum Albumin; D001710:Biotin; C027478:glucuronoxylomannan