Glanders Vaccine Developement

鼻疽疫苗开发

• 批准号: 8103209
• 负责人: Donald E. WOODS
• 金额: $ 6.17万
• 依托单位: UNIVERSITY OF CALGARY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8103209
• 关键词: 3-Dimensional; Animals; Antibody Formation; Area; Australia; Bacterial Adhesins; Biological Warfare; Bioterrorism; Burkholderia mallei; Burkholderia pseudomallei; Carrier Proteins; Categories; Centers for Disease Control and Prevention (U.S.); Conjugate Vaccines; DCNU; Development; Disaccharides; Disease; Emerging Communicable Diseases; Epithelial Cells; Equus caballus; Exotoxins; Family; Glanders; Human; Immune response; Immunotherapeutic agent; Inbred BALB C Mice; Infection; Intervention; Lipopolysaccharides; Malleus; Melioidosis; Modeling; Mus; Needles; O Antigens; Organism; Pathogenesis; Play; Polysaccharides; Positioning Attribute; Prevention; Prevention approach; Proteins; Recombinants; Role; Serum; Structure; Surface; Surface Antigens; System; Testing; Thailand; Vaccines; Virulence; base; capsule; extracellular; member; mouse model; prevent; vaccine candidate

DESCRIPTION (provided by applicant): Our broad, long-term objectives are to develop human vaccines for the prevention of glanders caused by Burkholderia mallei, and for melioidosis caused by B. pseudomallei. In the currently proposed studies, we will examine the immune response to B. mallei and B. pseudomallei vaccine candidates in small animals and in the horse, and we will determine the efficacy of immunotherapeutic interventions in challenge studies with an aim toward developing plans for extending the results to a human vaccine. The major hypothesis being evaluated is that immunotherapeutic intervention is a viable approach for the prevention of glanders caused by B. mallei and for the prevention of melioidosis caused by the closely related organism, B. pseudomallei. We have made significant progress in the last number of years in the identification of the virulence determinants of B. mallei and B. pseudomallei which we hypothesize will be excellent candidates as components of conjugate vaccines. Of particular note are two polysaccharide structures present on the surface of both of these organisms which are critical for the virulence of both of these. These are an extracellular polysaccharide capsule (CPS) and lipopolysaccharide O-antigen (OPS). We propose to conjugate the CPS and OPS polysaccharides to six carrier proteins shown or predicted to play important roles in pathogenesis by B. pseudomallei and B. mallei. CPS and OPS will also be conjugated to recombinant exotoxin A, a proven efficacious carrier protein of polysaccharide-based vaccines. We believe that this strategy will identify a vaccine that will protect against B. mallei challenge in a mouse model of infection as well as against B. mallei challenge in the horse which is the natural host for the organism. If shown to be successful in preventing glanders, this vaccine will be subsequently used in human trials to investigate protection against melioidosis in Australia and Thailand. Our specific aims are: 1. To evaluate the immune response to CPS and OPS conjugated to the carrier proteins in mice and in the horse. 2. To determine the ability of CPS and OPS conjugated to the carrier proteins to protect against B. mallei challenge in a BALB/c mouse model of infection. 3. To test the hypothesis that CPS and OPS conjugates which are protective in BALB/c mice will also protect the horse against B. mallei challenge. We believe that immunotherapeutic intervention is a viable approach for the prevention of glanders caused by B. mallei and for the prevention of melioidosis caused by the closely related organism, B. pseudomallei. Since B. mallei and B. pseudomallei are of significance as agents of bioterrorism (Category B, Centers for Disease Control, U.S.) and biological warfare, the development of effective vaccines are of particular concern. Vaccines will also have considerable multi-use potential since the diseases caused by these organisms are recognized as emerging infectious diseases in various areas of the world.

描述（由申请人提供）： 我们广泛的长期目标是开发人类疫苗，用于预防鼻疽伯克霍尔德氏菌引起的鼻疽和B引起的类鼻疽。假鼻疽在目前提出的研究中，我们将检查对B的免疫应答。鼻疽和B.我们将在小动物和马中确定类鼻疽疫苗候选物，并且我们将在挑战研究中确定免疫干预的功效，旨在制定将结果扩展到人类疫苗的计划。正在评估的主要假设是，免疫干预是预防B引起的鼻疽的可行方法。鼻疽和预防由密切相关的生物体B引起的类鼻疽。假鼻疽在过去的几年里，我们在鉴定B的毒力决定因子方面取得了重大进展。鼻疽和B.我们假设其将是作为结合疫苗的组分的优异候选物。特别值得注意的是存在于这两种生物体的表面上的两种多糖结构，其对于这两种生物体的毒力是至关重要的。它们是胞外多糖囊（CPS）和脂多糖O-抗原（OPS）。我们建议将CPS和OPS多糖缀合到B显示或预测在发病机制中起重要作用的六种载体蛋白。类鼻疽和B.鼻疽CPS和OPS还将与重组外毒素A缀合，重组外毒素A是基于多糖的疫苗的经证实的有效载体蛋白。我们相信，这一战略将确定一种疫苗，将防止B。在感染的小鼠模型中以及针对B的鼻疽攻击。马的鼻疽挑战，马是有机体的天然宿主。如果证明能成功预防鼻疽，这种疫苗随后将用于人体试验，以研究澳大利亚和泰国对类鼻疽的保护作用。我们的具体目标是：1.评价小鼠和马对与载体蛋白缀合的CPS和OPS的免疫应答。2.确定CPS和OPS与载体蛋白结合的抗B能力。在BALB/c小鼠感染模型中进行鼻疽菌攻击。3.检验在BALB/c小鼠中具有保护作用的CPS和OPS结合物也将保护马免受B侵害的假设。鼻疽挑战。我们相信免疫干预是预防B引起鼻疽的可行方法。鼻疽和预防由密切相关的生物体B引起的类鼻疽。假鼻疽从B开始。鼻疽和B.类鼻疽是重要的生物恐怖主义因子（类别B，美国疾病控制中心）。和生物战，有效疫苗的开发尤其令人关切。疫苗还将具有相当大的多用途潜力，因为这些生物体引起的疾病被认为是世界各地新出现的传染病。

项目成果

Capsule influences the deposition of critical complement C3 levels required for the killing of Burkholderia pseudomallei via NADPH-oxidase induction by human neutrophils.

• DOI: 10.1371/journal.pone.0052276
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Woodman ME;Worth RG;Wooten RM
• 通讯作者: Wooten RM