Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy.
Vaccine. 2010 Mar 19;28(14):2615-23. doi: 10.1016/j.vaccine.2010.01.012. Epub 2010 Jan 21.
A laminarin-diphtheria toxoid (CRM197) conjugate vaccine conferred protection against fungal infections in mice. We have now generated novel beta-glucan-CRM197 vaccines, with either natural (Curd-CRM197) or synthetic linear (15mer-CRM197), or beta-(1,6)-branched (17mer-CRM197) beta-(1,3)-oligosaccharides, formulated with the human-acceptable adjuvant MF59. Curd-CRM197 and 15mer-CRM197 conjugates, which induced high titers of anti-beta-(1,3)-glucan IgG, but no antibodies against beta-(1,6)-glucan, conferred protection to mice lethally challenged with C. albicans. In contrast, the 17mer-CRM197 conjugate, which induced anti-beta-(1,6)-glucan antibodies in addition to the anti-beta-(1,3)-glucan IgG, was non-protective. These data provide some insights on beta-glucan epitope(s) mediating antifungal protection and open the way to develop a synthetic oligosaccharide vaccine against fungal diseases.
一种裂褶多糖-白喉类毒素（CRM197）缀合物疫苗可预防小鼠真菌感染。我们现在已经生成了新型β-葡聚糖-CRM197 疫苗，分别使用天然（凝乳-CRM197）或合成线性（15mer-CRM197）或β-（1,6）-支链（17mer-CRM197）β-（1,3）-寡糖，并与可接受的人类佐剂 MF59 配制。凝乳-CRM197 和 15mer-CRM197 缀合物诱导了针对β-（1,3）-葡聚糖 IgG 的高滴度抗体，但不诱导针对β-（1,6）-葡聚糖的抗体，可对致死性白念珠菌挑战的小鼠提供保护。相比之下，17mer-CRM197 缀合物除了诱导抗β-（1,3）-葡聚糖 IgG 外，还诱导抗β-（1,6）-葡聚糖抗体，但其没有保护作用。这些数据提供了一些关于介导抗真菌保护的β-葡聚糖表位的见解，并为开发针对真菌病的合成寡糖疫苗开辟了道路。
