Beta-glucan-CRM197 conjugates as candidates antifungal vaccines

Beta-glucan-CRM197 conjugates as candidates antifungal vaccines
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DOI:
10.1016/j.vaccine.2010.01.012
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发表时间:
2010-03-19
期刊:
影响因子:
5.5
通讯作者:
Cassone, Antonio
Cassone, Antonio
中科院分区:
医学3区
文献类型:
--
作者:
Bromuro, Carla;Romano, Maria;Cassone, Antonio

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昆布多糖-白喉类毒素(CRM 197)缀合物疫苗在小鼠中赋予针对真菌感染的保护。我们现在已经产生了新型β-葡聚糖-CRM 197疫苗,其具有天然(Curd-CRM 197)或合成的线性(15 mer-CRM 197)或β-(1,6)-支链(17 mer-CRM 197)β-(1,3)-寡糖,与人类可接受的佐剂MF 59一起配制。凝乳-CRM 197和15聚体-CRM 197结合物诱导高滴度的抗β-(1,3)-葡聚糖IgG,但不诱导抗β-(1,6)-葡聚糖的抗体,对用C.白色念珠菌相比之下,除了抗β-(1,3)-葡聚糖IgG之外还诱导抗β-(1,6)-葡聚糖抗体的17聚体-CRM 197缀合物是非保护性的。这些数据为β-葡聚糖表位介导抗真菌保护提供了一些见解,并为开发针对真菌疾病的合成寡糖疫苗开辟了道路。(C)2010爱思唯尔有限公司版权所有。
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. (C) 2010 Elsevier Ltd. All rights reserved.