Isolation and characterisation of monoclonal antibodies for the treatment or prevention of antibiotic resistant Acinetobacter baumannii infections
用于治疗或预防抗生素耐药鲍曼不动杆菌感染的单克隆抗体的分离和表征
基本信息
- 批准号:MR/Y008693/1
- 负责人:
- 金额:$ 197.22万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2024
- 资助国家:英国
- 起止时间:2024 至 无数据
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
The bacteria Acinetobacter baumannii causes severe lung and blood-borne infections in humans. It is one of the most highly resistant bacteria to antibiotics, and as a consequence A. baumannii infections have a very high mortality which approaches 50%. Overall, A. baumannii causes over 50,000 deaths per year across the globe, a number which is increasing. It is especially common in Asia with 15,000 deaths per year in Thailand alone, and at one of our research site hospitals the number of people with A. baumannii per year has increased from 100 in 2010 to over 500 in 2022. The World Health Organisation has made A. baumannii its top priority antibiotic resistant bacteria for which we need new treatments. One way of overcoming antibiotic resistance is to treat bacteria with antibodies, naturally occurring proteins that bind to invading microbes and boost the ability of the immune system to kill them. Antibody therapies are known to work for other microbes but are not available as yet for A. baumannii. We aim to fill this gap by developing an antibody treatment for A. baumannii. Over the past four years, we have identified antibodies to four A. baumannii proteins that we have shown bind strongly to the bacterial surface and can increase activity of the immune system against the bacteria. Importantly when given to mice these antibodies protected against A. baumannii infection, indicating they could be a good treatment for human infection. We now want to develop these antibodies for use in humans. To do so we need to obtain single specific antibodies for each of our protein targets which are called monoclonal antibodies, as these can then be produced in a factory in the large quantities needed for a treatment. We will isolate several monoclonal antibodies to each of our four A. baumannii proteins from either humans who have had previous A. baumannii infection and have developed an immune response to this bacteria, or from mice using vaccination experiments. We will then test each isolated monoclonal antibody to see how well they bind to and promote the immune systems ability to recognise and kill A. baumannii strains. We will also test each monoclonal antibody to see whether they can protect mice against A. baumannii infection. The most effective monoclonal antibodies will then be tested in combinations as our previous work suggests this will be more effective than a single antibody. In addition, we will collect data and samples on patients with A. baumannii infection at our hospital research site in Thailand. The information on the patients is needed so we can plan future clinical trials of a monoclonal antibody therapy; and samples from the patients will also help with the experiments investigating the monoclonal antibodies by providing white cells from which we can isolate monoclonal antibodies. At the end of the study we will have the data needed to decide which of the monoclonal antibodies and in which combination are likely to be the most effective treatment for A. baumannii infections. These monoclonal antibodies will in the future be developed into a clinical treatment for testing in humans.
鲍氏不动杆菌可引起人类严重的肺部和血液传播感染。它是对抗生素最具耐药性的细菌之一,因此A.鲍曼不动杆菌感染具有非常高的死亡率,接近50%。总体而言,A.鲍曼不动杆菌每年在地球仪造成50 000多人死亡,这个数字还在增加。它在亚洲尤其常见,仅在泰国每年就有15,000人死亡,在我们的一家研究中心医院,A.每年的鲍曼不动杆菌数量从2010年的100个增加到2022年的500多个。世界卫生组织(WHO)已将A。鲍曼不动杆菌是首要抗生素耐药细菌,我们需要新的治疗方法。克服抗生素耐药性的一种方法是用抗体治疗细菌,抗体是天然存在的蛋白质,可以与入侵的微生物结合,提高免疫系统杀死它们的能力。已知抗体疗法对其他微生物有效,但对A.鲍曼不动杆菌。我们的目标是通过开发A的抗体治疗来填补这一空白。鲍曼不动杆菌。在过去的四年里,我们已经确定了四种A的抗体。我们已经展示的鲍曼不动杆菌蛋白质与细菌表面强烈结合,并且可以增加免疫系统对抗细菌的活性。重要的是,当给予小鼠时,这些抗体可以保护小鼠免受A.鲍曼不动杆菌感染,表明它们可能是治疗人类感染的良好药物。我们现在想开发这些抗体用于人类。要做到这一点,我们需要获得针对每种蛋白质靶点的单一特异性抗体,这些抗体被称为单克隆抗体,因为这些抗体可以在工厂中大量生产用于治疗。我们将分离出几个单克隆抗体,以我们的四个A。鲍曼不动杆菌蛋白来自于先前患有A.鲍曼不动杆菌感染,并已发展出免疫反应,这种细菌,或从小鼠使用疫苗接种实验。然后,我们将测试每一个分离的单克隆抗体,看看他们如何结合,并促进免疫系统的能力,以识别和杀死A。鲍曼不动杆菌。我们还将测试每种单克隆抗体,看看它们是否能保护小鼠免受A。鲍曼不动杆菌感染最有效的单克隆抗体将在组合中进行测试,因为我们以前的工作表明这将比单一抗体更有效。此外,我们将收集A型糖尿病患者的数据和样本。鲍曼不动杆菌感染在我们的医院研究地点在泰国。需要患者的信息,以便我们可以计划未来的单克隆抗体治疗临床试验;患者的样本也将有助于研究单克隆抗体的实验,因为我们可以提供白色细胞,从中分离单克隆抗体。在研究结束时,我们将获得所需的数据,以决定哪种单克隆抗体和哪种组合可能是治疗A的最有效方法。鲍曼不动杆菌感染。这些单克隆抗体将来将被开发成用于人体测试的临床治疗。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jeremy Brown其他文献
TYM (Test Your Memory) Testing
TYM(测试你的记忆力)测试
- DOI:
10.1007/978-1-4471-2452-8_9 - 发表时间:
2013 - 期刊:
- 影响因子:0
- 作者:
Jeremy Brown - 通讯作者:
Jeremy Brown
Impaired C3b/iC3b deposition on Streptococcus pneumoniae in serum from patients with systemic lupus erythematosus.
系统性红斑狼疮患者血清中肺炎链球菌上的 C3b/iC3b 沉积受损。
- DOI:
10.1093/rheumatology/kep289 - 发表时间:
2009 - 期刊:
- 影响因子:5.5
- 作者:
F. Goldblatt;J. Yuste;D. Isenberg;Anisur Rahman;Jeremy Brown - 通讯作者:
Jeremy Brown
A marriage of convenience? A qualitative study of colleague supervision of master's level dissertations
- DOI:
10.1016/j.nedt.2010.12.025 - 发表时间:
2011-11-01 - 期刊:
- 影响因子:
- 作者:
Jennifer Kirton;Katherine Straker;Jeremy Brown;Barbara Jack;Annette Jinks - 通讯作者:
Annette Jinks
Efficient LiDAR-Based Object Segmentation and Mapping for Maritime Environments
适用于海洋环境的基于 LiDAR 的高效对象分割和测绘
- DOI:
- 发表时间:
2019 - 期刊:
- 影响因子:4.1
- 作者:
D. Thompson;E. Coyle;Jeremy Brown - 通讯作者:
Jeremy Brown
Differential Expression of Cell Surface Markers by Ovine Respiratory Tract Dendritic Cells
绵羊呼吸道树突状细胞细胞表面标志物的差异表达
- DOI:
- 发表时间:
2006 - 期刊:
- 影响因子:3.2
- 作者:
T. McNeilly;Jeremy Brown;G. Harkiss - 通讯作者:
G. Harkiss
Jeremy Brown的其他文献
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{{ truncateString('Jeremy Brown', 18)}}的其他基金
Identifying the correlates of protection against Streptococcus pneumoniae respiratory tract infection using a human challenge model
使用人体挑战模型确定预防肺炎链球菌呼吸道感染的相关性
- 批准号:
MR/Z503721/1 - 财政年份:2024
- 资助金额:
$ 197.22万 - 项目类别:
Research Grant
Travel: Improving the Utility of Haptic Feedback in Upper-Limb Prosthesis Control: Establishing user-centric guidelines for engineering innovation
旅行:提高上肢假肢控制中触觉反馈的效用:建立以用户为中心的工程创新指南
- 批准号:
2331318 - 财政年份:2023
- 资助金额:
$ 197.22万 - 项目类别:
Standard Grant
CAREER: Improving Prosthesis Usability through Enhanced Touch Feedback and Intelligent Control
职业:通过增强的触摸反馈和智能控制提高假肢的可用性
- 批准号:
2146206 - 财政年份:2022
- 资助金额:
$ 197.22万 - 项目类别:
Standard Grant
Collaborative Research: OPUS: CRS: A Synthetic View of Evolutionary Heterogeneity and the Tree of Life
合作研究:OPUS:CRS:进化异质性和生命之树的综合观点
- 批准号:
1950759 - 财政年份:2020
- 资助金额:
$ 197.22万 - 项目类别:
Standard Grant
Collaborative Research: CIBR: CloudForest: A Portable Cyberinfrastructure Workflow To Advance Biological Insight from Massive, Heterogeneous Phylogenomic Datasets
合作研究:CIBR:CloudForest:一种便携式网络基础设施工作流程,可从海量、异质的系统发育数据集中推进生物学洞察
- 批准号:
1934156 - 财政年份:2019
- 资助金额:
$ 197.22万 - 项目类别:
Standard Grant
CHS: Small: Understanding Environment Perception and Task Performance in Human-in-the-Loop Tele-robotic Systems (HiLTS)
CHS:小型:了解人在环远程机器人系统 (HiLTS) 中的环境感知和任务性能
- 批准号:
1910939 - 财政年份:2019
- 资助金额:
$ 197.22万 - 项目类别:
Continuing Grant
Adjunct antibody therapy for severe antibiotic-resistant Acinetobacter baumannii infections
严重抗生素耐药鲍曼不动杆菌感染的辅助抗体治疗
- 批准号:
MR/S004394/1 - 财政年份:2018
- 资助金额:
$ 197.22万 - 项目类别:
Research Grant
Universal protection against Streptococcus pneumoniae by recombinant glycoconjugate vaccines
重组糖复合物疫苗对肺炎链球菌具有普遍保护作用
- 批准号:
MR/R001871/1 - 财政年份:2018
- 资助金额:
$ 197.22万 - 项目类别:
Research Grant
Adjunct antibody therapy for severe antibiotic-resistant Acinetobacter baumannii infections
严重抗生素耐药鲍曼不动杆菌感染的辅助抗体治疗
- 批准号:
MC_PC_17227 - 财政年份:2018
- 资助金额:
$ 197.22万 - 项目类别:
Intramural
Training in Innovative Phylogenetics and Comparative Methods at the Society of Systematic Biologists Meeting, January, 2017, Baton Rouge, Louisiana
系统生物学家协会会议上的创新系统发育学和比较方法培训,2017 年 1 月,路易斯安那州巴吞鲁日
- 批准号:
1723656 - 财政年份:2017
- 资助金额:
$ 197.22万 - 项目类别:
Standard Grant
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