Development of capsular polysaccharide-based glycoconjugates for immunization against melioidosis and glanders.

Development of capsular polysaccharide-based glycoconjugates for immunization against melioidosis and glanders.
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开发基于荚膜多糖的糖复合物,用于针对类鼻疽和鼻疽的免疫。

DOI:
10.3389/fcimb.2012.00108
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发表时间:
2012
影响因子:
5.7
通讯作者:
Brett PJ
Brett PJ
中科院分区:
医学2区
文献类型:
--
作者:
Burtnick MN;Heiss C;Roberts RA;Schweizer HP;Azadi P;Brett PJ

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类鼻疽伯克霍尔德氏菌和马来伯克霍尔德氏菌分别是类鼻疽和扁桃体的病原体,可引起人类和动物的严重疾病,被认为是生物战和恐怖主义的潜在病原体。这些病原体引起的感染的诊断和治疗可能具有挑战性,在没有化疗干预的情况下,急性疾病往往是致命的。目前,没有人或兽医疫苗可用于对这些新出现/重新出现的传染病进行免疫接种。因此,我们研究的长期目标之一是鉴定和鉴定假单胞菌和马来双胞菌表达的保护性抗原,并利用它们来开发有效的候选疫苗。以往的研究表明,这些细菌表达的6-脱氧庚烷胶囊多糖(CPS)既是毒力决定簇,又是保护性抗原。因此,这种碳水化合物部分已成为我们实验室目前正在开发的各种亚单位疫苗的重要组成部分。在本研究中,我们描述了一种从O-多糖(OPS)缺乏的假鼻疽杆菌菌株中分离CPS抗原的可靠方法;该方法包括选择剂排除菌株Bp82的衍生物。利用这些纯化的CPS样本,我们还描述了一种简单的程序,将这些T细胞非依赖抗原与载体蛋白共价连接。此外,我们还证明了针对这种构建物的CPS成分可以产生高滴度的免疫球蛋白G反应。总而言之,这些方法为开发新型的基于CPS的糖结合物提供了一个切实的起点,用于预防类鼻疽和腺体的免疫。
Burkholderia pseudomallei and Burkholderia mallei, the etiologic agents of melioidosis and glanders, respectively, cause severe disease in humans and animals and are considered potential agents of biological warfare and terrorism. Diagnosis and treatment of infections caused by these pathogens can be challenging and, in the absence of chemotherapeutic intervention, acute disease is frequently fatal. At present, there are no human or veterinary vaccines available for immunization against these emerging/re-emerging infectious diseases. One of the long term objectives of our research, therefore, is to identify and characterize protective antigens expressed by B. pseudomallei and B. mallei and use them to develop efficacious vaccine candidates. Previous studies have demonstrated that the 6-deoxy-heptan capsular polysaccharide (CPS) expressed by these bacterial pathogens is both a virulence determinant and a protective antigen. Consequently, this carbohydrate moiety has become an important component of the various subunit vaccines that we are currently developing in our laboratory. In the present study, we describe a reliable method for isolating CPS antigens from O-polysaccharide (OPS) deficient strains of B. pseudomallei; including a derivative of the select agent excluded strain Bp82. Utilizing these purified CPS samples, we also describe a simple procedure for covalently linking these T-cell independent antigens to carrier proteins. In addition, we demonstrate that high titer IgG responses can be raised against the CPS component of such constructs. Collectively, these approaches provide a tangible starting point for the development of novel CPS-based glycoconjugates for immunization against melioidosis and glanders.
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发表时间: 1997-04-01
影响因子: 3.2
作者:
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通讯作者: Woods, DE
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