新型隐球菌荚膜葡糖醛酸木甘露聚糖寡糖结构糖缀合物的合成及免疫学研究

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

作者信息

Oscarson Stefan, Alpe Mia, Svahnberg Pär, Nakouzi Antonio, Casadevall Arturo

机构信息

Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, S-106 91 Stockholm, Sweden.

出版信息

Vaccine. 2005 Jun 10;23(30):3961-72. doi: 10.1016/j.vaccine.2005.02.029. Epub 2005 Mar 24.

DOI:10.1016/j.vaccine.2005.02.029

PMID:15917118

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.

摘要

针对新型隐球菌多糖荚膜的葡糖醛酸木甘露聚糖（GXM）成分的抗体具有保护作用，并且GXM-蛋白质结合疫苗可引发保护性免疫反应。我们报告了一种七糖寡糖的合成，该寡糖代表血清型A GXM的推定主要基序，并证明它可被一些针对GXM产生的单克隆抗体（mAb）识别。将七糖与人血清白蛋白（HSA）偶联产生了一种免疫原性化合物，当与完全弗氏佐剂一起给予时，该化合物在小鼠中引发了高滴度的IgG反应。寡糖结合疫苗引发的抗体反应具有T细胞依赖性反应的特征。一种代表GXM结构基序的免疫原性寡糖的可用性将被证明在抗体表位特异性研究中有用，并且代表了一种针对这种真菌病原体的潜在合成寡糖疫苗。