A Synthetic Oligosaccharide Resembling Francisella tularensis Strain 15 O-Antigen Capsular Polysaccharide as a Lead for Tularemia Diagnostics and Therapeutics
Peter H. Seeberger, Kabita Pradhan, Emelie E. Reuber, Eric T. Sletten, Herbert Tomaso
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引用次数: 0
Abstract
Francisella tularensis, a category A bioterrorism agent, causes tularemia in many animal species. F. tularensis subspecies tularensis (type A) and holarctica (type B) are mainly responsible for human tularemia. The high mortality rate of 30-60% caused by F. tularensis subspecies tularensis if left untreated and the aerosol dispersal renders this pathogen a dangerous bioagent. While a live attenuated vaccine strain (LVS) of F. tularensis type B does not provide sufficient protection against all forms of tularemia infections, a significant level of protection against F. tularensis has been observed for both passive and active immunization of mice with isolated O-antigen capsular polysaccharide. Well-defined, synthetic oligosaccharides offer an alternative approach towards the development of glycoconjugate vaccines. To identify diagnostics and therapeutics leads against tularemia, a collection of F. tularensis strain 15 O-antigen capsular polysaccharide epitopes were chemically synthesized. Glycan microarrays containing synthetic glycans were used to analyze the sera of tularemia-infected and non-infected animals and revealed the presence of IgG antibodies against the glycans. Two disaccharide (13 and 18), both bearing a unique formamido moiety, were identified as minimal glycan epitopes for antibody binding. These epitopes are the starting point for the development of diagnostics and therapeutics against tularemia.
土拉菌属弗朗西斯菌是一种 A 类生物恐怖剂,可导致多种动物患上土拉菌病。土拉菌亚种(A 型)和 Holarctica(B 型)是人类土拉菌病的主要致病菌。土拉菌亚种如果不及时治疗,死亡率高达 30-60%,而且会通过气溶胶扩散,因此这种病原体是一种危险的生物制剂。虽然 B 型土拉菌减毒活疫苗菌株(LVS)不能对所有形式的土拉菌病感染提供足够的保护,但用分离的 O 抗原荚膜多糖对小鼠进行被动免疫和主动免疫都能对土拉菌病产生显著的保护作用。定义明确的合成寡糖为开发糖结合疫苗提供了另一种方法。为了确定针对土拉菌病的诊断和治疗方法,我们用化学方法合成了一系列土拉菌 15 株 O 抗原荚膜多糖表位。用含有合成聚糖的聚糖微阵列分析土拉菌病感染动物和非感染动物的血清,结果显示存在针对聚糖的 IgG 抗体。两个双糖(13 和 18)都含有独特的甲酰氨基,被确定为抗体结合的最小聚糖表位。这些表位是开发针对土拉菌病的诊断和治疗方法的起点。
期刊介绍:
Angewandte Chemie, a journal of the German Chemical Society (GDCh), maintains a leading position among scholarly journals in general chemistry with an impressive Impact Factor of 16.6 (2022 Journal Citation Reports, Clarivate, 2023). Published weekly in a reader-friendly format, it features new articles almost every day. Established in 1887, Angewandte Chemie is a prominent chemistry journal, offering a dynamic blend of Review-type articles, Highlights, Communications, and Research Articles on a weekly basis, making it unique in the field.