Synthesis and immunological studies of glycoconjugates of Cryptococcus neoformans capsular glucuronoxylomannan oligosaccharide structures

Synthesis and immunological studies of glycoconjugates of Cryptococcus neoformans capsular glucuronoxylomannan oligosaccharide structures
June 10, 2005
Stefan Oscarson, a, Mia Alpe, a, P?r Svahnberg, a, Antonio Nakouzi, b and Arturo Casadevall, b
aDepartment of Organic Chemistry, Arrhenius Laboratory, Stockholm University, S-106 91 Stockholm, Sweden
bDivision of Infectious Diseases, Department of Medicine and the Department of Microbiology and Immunology, Albert Einstein College of Medicine, Golding Building, Room 701, 1300 Morris Park Avenue, Bronx, NY 10461, USA
Vaccine Volume 23, Issue 30 , 10 June 2005, Pages 3961-3972
ScienceDirect
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Abstract
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.