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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布鲁氏菌病：来自合成多糖的改进的诊断方法和疫苗见解

布鲁氏菌病是一种严重的人畜共患细菌病，被世界卫生组织列为威胁人类健康并造成贫困的七大“被忽视的人畜共患病”之一。它是一种代价高昂，具有高度传染性的疾病，会影响反刍动物，牛，绵羊，山羊和其他生产性动物（如猪）。症状包括流产，不育，产奶量减少，体重减轻和la行。布鲁氏菌病也是从动物传播给人类的最常见的细菌性疾病，每年约有50万例新的人类病例。由于目前仅疫苗接种还不够，因此需要对感染的动物进行检测和宰杀以根除该疾病。但是，由于最具保护性的疫苗会损害血清诊断，因此会造成政策难题，这些往往会导致根除和控制程序失败。检测抗光滑脂多糖的布鲁氏菌细菌细胞壁O-多糖（OPS）成分可用于诊断该疾病，并且同一分子对目前部署的兽用全细胞疫苗有重要的保护作用。这建立了一个长期的悖论，尽管布鲁切拉OPS赋予疫苗以保护作用，但它的存在会在受感染和接种疫苗的动物中产生相似的抗体谱。因此，不可能区分感染动物和疫苗接种动物（DIVA），这限制了与该疾病作斗争的努力。最近对布鲁氏菌属化学结构的澄清作为两个低聚糖序列的嵌段共聚物的OPS提供了利用独特的低聚糖的机会，这种独特的低聚糖只能通过化学合成在疾病的血清学诊断测试中获得。与目前的商业测试中使用的天然聚合物相比，这些寡糖显示出极好的敏感性和特异性，并具有辅助区分布鲁氏菌病和由OPS与布鲁氏菌共有结构特征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估过程中，很明显，存在一种机会来创造一种多糖-蛋白质结合疫苗，该疫苗不会产生在感染诊断测试中给出假阳性结果的抗体。该目标已付诸实践，对小鼠的免疫接种表明布鲁氏菌抗体可以在不基于M抗原的诊断测试中发生反应的情况下开发抗原。这种类型的结合疫苗可以很容易地开发用于人类和动物。但是，随着化学方法的发展和现代细菌工程方法​​的成熟，可以预期这些研究阐明的原理可以用于开发廉价和经济有效的疫苗来对抗动物流行性布鲁氏菌病。