Brucellosis: Improved Diagnostics and Vaccine Insights from Synthetic Glycans.
Brucellosis: Improved Diagnostics and Vaccine Insights from Synthetic Glycans.
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DOI：
10.1021/acs.accounts.7b00445
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发表时间：
2017-12-19
影响因子：
18.3
通讯作者：
McGiven J
中科院分区：
文献类型：
--
作者：
Bundle DR;McGiven J
布鲁氏菌病是一种严重的人畜共患细菌性疾病，被世界卫生组织列为威胁人类健康、造成贫困的七大“被忽视的人畜共患病”之一。这是一种代价高昂、高度传染性的疾病，影响反刍动物、牛、绵羊、山羊和其他生产性动物，如猪。症状包括流产、不孕、产奶量减少、体重减轻和跛行。布鲁氏菌病也是最常见的由动物传播给人类的细菌性疾病，每年约有50万例新发病例。需要检测和屠宰受感染的动物以根除该疾病，因为目前仅接种疫苗是不够的。然而，由于最具保护性的疫苗会危及血清诊断，这就造成了政策上的困境，而这往往会导致根除和控制计划的失败。布鲁氏菌细菌细胞壁O-多糖（OPS）组分的光滑脂多糖的抗体检测用于诊断这种疾病，相同的分子有助于目前部署的兽医全细胞疫苗的重要保护效力。这已经建立了一个长期存在的悖论，即虽然布鲁氏菌OPS赋予疫苗保护效力，但其存在导致感染和接种动物中相似的抗体谱。因此，不可能区分感染动物和接种动物（DIVA），这限制了防治疾病的努力。最近对布鲁氏菌OPS作为两个寡糖序列的嵌段共聚物的化学结构的澄清提供了在疾病的血清诊断测试中利用仅通过化学合成获得的独特寡糖的机会。与目前商业检测中使用的天然聚合物相比，这些寡糖显示出优异的灵敏度和特异性，并且具有辅助区分布鲁氏菌病和由具有与布鲁氏菌共享一些结构特征的OPS的几种细菌引起的感染的额外优势。在这些合成抗原的合成和免疫化学评价过程中，很明显存在产生多糖-蛋白质缀合物疫苗的机会，该疫苗不会产生在感染诊断试验中给出假阳性结果的抗体。这一目标被付诸实践，对小鼠的免疫接种表明，可以产生布鲁氏菌A抗原的抗体，而不会在基于M抗原的诊断试验中发生反应。这种类型的缀合物疫苗可以容易地开发用于人和动物。然而，随着化学方法的进步和现代细菌工程方法的成熟，预计这些研究阐明的原理可以应用于开发廉价且具有成本效益的疫苗，以对抗动物中的地方性布鲁氏菌病。
Brucellosis is a serious zoonotic bacterial disease that is ranked by the World Health Organization among the top seven “neglected zoonoses” that threaten human health and cause poverty. It is a costly, highly contagious disease that affects ruminants, cattle, sheep, goats, and other productive animals such as pigs. Symptoms include abortions, infertility, decreased milk production, weight loss, and lameness. Brucellosis is also the most common bacterial disease that is transmitted from animals to humans, with approximately 500 000 new human cases each year. Detection and slaughter of infected animals is required to eradicate the disease, as vaccination alone is currently insufficient. However, as the most protective vaccines compromise serodiagnosis, this creates policy dilemmas, and these often result in the failure of eradication and control programs. Detection of antibodies to the Brucella bacterial cell wall O-polysaccharide (OPS) component of smooth lipopolysaccharide is used in diagnosis of this disease, and the same molecule contributes important protective efficacy to currently deployed veterinary whole-cell vaccines. This has set up a long-standing paradox that while Brucella OPS confers protective efficacy to vaccines, its presence results in similar antibody profiles in infected and vaccinated animals. Consequently, differentiation of infected from vaccinated animals (DIVA) is not possible, and this limits efforts to combat the disease. Recent clarification of the chemical structure of Brucella OPS as a block copolymer of two oligosaccharide sequences has provided an opportunity to utilize unique oligosaccharides only available via chemical synthesis in serodiagnostic tests for the disease. These oligosaccharides show excellent sensitivity and specificity compared with the native polymer used in current commercial tests and have the added advantage of assisting discrimination between brucellosis and infections caused by several bacteria with OPS that share some structural features with those of Brucella. During synthesis and immunochemical evaluation of these synthetic antigens, it became apparent that an opportunity existed to create a polysaccharide–protein conjugate vaccine that would not create antibodies that give false positive results in diagnostic tests for infection. This objective was reduced to practice, and immunization of mice showed that antibodies to the Brucella A antigen could be developed without reacting in a diagnostic test based on the M antigen. A conjugate vaccine of this type could readily be developed for use in humans and animals. However, as chemical methods advance and modern methods of bacterial engineering mature, it is expected that the principles elucidated by these studies could be applied to the development of an inexpensive and cost-effective vaccine to combat endemic brucellosis in animals.
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DOI：
10.1128/cdli.5.6.862-870.1998
发表时间：
1998-11-01
期刊：
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY
影响因子：
--
作者：
Cloeckaert, A;Weynants, V;Zygmunt, MS
通讯作者：
Zygmunt, MS
影响因子：
3.1
作者：
CAROFF, M;BUNDLE, DR;DUNCAN, JR
通讯作者：
DUNCAN, JR
影响因子：
2.9
作者：
BUNDLE, DR;CHERWONOGRODZKY, JW;PERRY, MB
通讯作者：
PERRY, MB
影响因子：
18.2
作者：
Mandal, Satadru Sekhar;Duncombe, Lucy;McGiven, John
通讯作者：
McGiven, John
影响因子：
16.6
作者：
Guiard, Julie;Paszkiewicz, Eugenia;Bundle, David R.
通讯作者：
Bundle, David R.