MICA: Study of disease mechanisms in enteric fever to characterise innate & adaptive immunity in mucosa & blood in controlled human infection model
MICA:研究肠热症的疾病机制以表征先天性
基本信息
- 批准号:MR/K021222/1
- 负责人:
- 金额:$ 467.22万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2013
- 资助国家:英国
- 起止时间:2013 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Typhoid fever (also known as enteric fever), an infection characterised by diarrhoea and rash, is most often caused by a type of bacteria called Salmonella enterica. After gaining entry to the body via contaminated food or drink, the Salmonellae travel first to the gut, and then the bloodstream, from where they can infect the lymph nodes, gallbladder, liver, spleen, and other parts of the body. Treatment of enteric fever is by rehydration either intravenously or by drinking uncontaminated water mixed with electrolytes. Antibiotics are used to kill the bacteria, but as there are increasing rates of antibiotic resistant S. enterica throughout the world, this means of treatment is becoming less effective. Two Salmonella variants, known as serovars Typhi and Paratyphi, cause around 27 million cases of enteric fever and more than 200,000 deaths per year worldwide, mostly in the developing countries. Even though improved sanitation through economic development should eventually eliminate enteric fever, reduction of the disease burden in the medium term is achievable through effective immunisation, especially in the face of increasing antibiotic resistance.Although effective vaccines are likely to be available for mass vaccination against typhoid in the near future, these vaccines will be effective only against those strains of S. Typhi and S. Paratyphi that bear the Vi polysaccaharide capsule proteins. Strains that do not have these capsule proteins, or that have no capsule (acapsulate) will be unaffected by vaccination and could fill the ecological space vacated by the capsulate strains. Indeed, enteric fever caused by S. Paratyphi A which does not carry the Vi protein and for which there is currently no vaccine, has risen during the past decade and accounts for more than half of all cases in some areas. Thus it is important that effective vaccines are available to protect against infection by both capsulated and non-encapsulated Salmonella enterica. To develop such vaccines, we need a full understanding of the human immune response to the acapsulate Salmonella including the interactions between the inbuilt immune system and disease-specific immunity, contributions of immunity in the gut and the bloodstream, immune response to protein and to polysaccharide determinants, and the role of antibodies. How much cross-protection there is between capsulate and non-capsulate typhoidal Salmonellae after natural infection or vaccination is not known, but this is critically important to vaccine development.With this project we aim to fill in the knowledge gaps highlighted above, by fully characterising the infection process and immune response in enteric fever.
伤寒(又称肠热病)是一种以腹泻和皮疹为特征的感染,最常见的是由一种名为肠道沙门氏菌的细菌引起的。在通过受污染的食物或饮料进入人体后,沙门氏菌首先进入肠道,然后进入血液,从那里它们可以感染淋巴、胆囊、肝脏、脾和身体的其他部位。肠热病的治疗方法是静脉补液或饮用混合了电解质的未受污染的水。抗生素是用来杀死细菌的,但随着世界各地对抗生素耐药的肠球菌的比率不断上升,这种治疗方法变得越来越不有效。两种沙门氏菌变种,即伤寒和副伤寒,每年在全球范围内造成约2700万例肠热病病例和20多万人死亡,其中大部分发生在发展中国家。尽管通过经济发展改善卫生条件最终应该会消除肠热病,但在中期内,通过有效的免疫接种可以减少疾病负担,特别是在抗生素耐药性日益增强的情况下。虽然有效的疫苗很可能在不久的将来用于大规模接种伤寒疫苗,但这些疫苗只对携带Vi多聚糖核酸衣壳蛋白的伤寒和副伤寒沙门氏菌株有效。没有这些被膜蛋白的菌株或没有被膜(囊壳)的菌株将不会受到疫苗接种的影响,并可能填补被被包膜菌株腾出的生态空间。事实上,甲型副伤寒沙门氏菌引起的肠热病在过去十年中有所上升,在某些地区占所有病例的一半以上。甲型副伤寒沙门氏菌不携带Vi蛋白,目前还没有疫苗。因此,重要的是要有有效的疫苗,以预防被囊化和未被囊化的肠炎沙门氏菌感染。为了开发这样的疫苗,我们需要充分了解人类对包囊沙门氏菌的免疫反应,包括内置免疫系统和疾病特异性免疫之间的相互作用,肠道和血液中免疫的贡献,对蛋白质和多糖决定因素的免疫反应,以及抗体的作用。在自然感染或接种伤寒沙门氏菌后,包膜和非包膜的伤寒沙门氏菌之间有多少交叉保护尚不清楚,但这对疫苗的开发至关重要。通过这个项目,我们的目标是通过全面描述肠热病的感染过程和免疫反应来填补上面强调的知识空白。
项目成果
期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Homologous and heterologous re-challenge with Salmonella Typhi and Salmonella Paratyphi A in a randomised controlled human infection model.
- DOI:10.1371/journal.pntd.0008783
- 发表时间:2020-10
- 期刊:
- 影响因子:3.8
- 作者:Gibani MM;Jin C;Shrestha S;Moore M;Norman L;Voysey M;Jones E;Blackwell L;Thomaides-Brears H;Hill J;Blohmke CJ;Dobinson HC;Baker P;Jones C;Campbell D;Mujadidi YF;Plested E;Preciado-Llanes L;Napolitani G;Simmons A;Gordon MA;Angus B;Darton TC;Cerundulo V;Pollard AJ
- 通讯作者:Pollard AJ
The Impact of Vaccination and Prior Exposure on Stool Shedding of Salmonella Typhi and Salmonella Paratyphi in 6 Controlled Human Infection Studies.
- DOI:10.1093/cid/ciy670
- 发表时间:2019-04-08
- 期刊:
- 影响因子:0
- 作者:Gibani MM;Voysey M;Jin C;Jones C;Thomaides-Brears H;Jones E;Baker P;Morgan M;Simmons A;Gordon MA;Cerundolo V;Pitzer VE;Angus B;Levine MM;Darton TC;Pollard AJ
- 通讯作者:Pollard AJ
Sterile activation of invariant natural killer T cells by ER-stressed antigen-presenting cells
- DOI:10.1073/pnas.1910097116
- 发表时间:2019-11-19
- 期刊:
- 影响因子:11.1
- 作者:Bedard, Melissa;Shrestha, Dilip;Cerundolo, Vincenzo
- 通讯作者:Cerundolo, Vincenzo
Immune checkpoint inhibitor-related colitis assessment and prognosis: can IBD scoring point the way?
- DOI:10.1038/s41416-020-0882-y
- 发表时间:2020-05-18
- 期刊:
- 影响因子:8.8
- 作者:Cheung, Vincent Ting Fung;Gupta, Tarun;Brain, Oliver
- 通讯作者:Brain, Oliver
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Vincenzo Cerundolo其他文献
IFN-gamma exposes a cryptic cytotoxic T lymphocyte epitope in HIV-1 reverse transcriptase.
IFN-γ 暴露了 HIV-1 逆转录酶中隐藏的细胞毒性 T 淋巴细胞表位。
- DOI:
- 发表时间:
1999 - 期刊:
- 影响因子:4.4
- 作者:
Andrew K. Sewell;David Price;H. Teisserenc;B. Booth;U. Gileadi;F. Flavin;John Trowsdale;R. Phillips;Vincenzo Cerundolo - 通讯作者:
Vincenzo Cerundolo
Formulation de composants mycobactériens comme adjuvant pour induire des réponses th17
分枝杆菌复合佐剂配方 17
- DOI:
- 发表时间:
2013 - 期刊:
- 影响因子:0
- 作者:
A. Sher;Kevin Shenderov;Vincenzo Cerundolo;G. S. Besra - 通讯作者:
G. S. Besra
MAIT cells activate dendritic cells to promote TsubFH/sub cell differentiation and induce humoral immunity
MAIT 细胞激活树突状细胞以促进 TsubFH/sub 细胞分化并诱导体液免疫
- DOI:
10.1016/j.celrep.2023.112310 - 发表时间:
2023-04-25 - 期刊:
- 影响因子:6.900
- 作者:
Theresa E. Pankhurst;Kaitlin H. Buick;Joshua L. Lange;Andrew J. Marshall;Kaileen R. Button;Olga R. Palmer;Kathryn J. Farrand;Isabelle Montgomerie;Thomas W. Bird;Ngarangi C. Mason;Joanna Kuang;Benjamin J. Compton;Davide Comoletti;Mariolina Salio;Vincenzo Cerundolo;Miguel E. Quiñones-Mateu;Gavin F. Painter;Ian F. Hermans;Lisa M. Connor - 通讯作者:
Lisa M. Connor
Remodelling of the immune landscape by IFNγ counteracts IFNγ-dependent tumour escape in mouse tumour models
IFNγ 重塑免疫景观可抵消小鼠肿瘤模型中依赖 IFNγ 的肿瘤逃逸
- DOI:
10.1038/s41467-024-54791-0 - 发表时间:
2025-01-02 - 期刊:
- 影响因子:15.700
- 作者:
Vivian W. C. Lau;Gracie J. Mead;Zofia Varyova;Julie M. Mazet;Anagha Krishnan;Edward W. Roberts;Gennaro Prota;Uzi Gileadi;Kim S. Midwood;Vincenzo Cerundolo;Audrey Gérard - 通讯作者:
Audrey Gérard
352: Analysis of Renal Cell Cancer Tumour Antigen Carbonic Anhydrase 9 Specific Cytotoxic T Lymphocytes from a Healthy HLA-A2 Donor
- DOI:
10.1016/s0022-5347(18)34605-6 - 发表时间:
2005-04-01 - 期刊:
- 影响因子:
- 作者:
Tsung Wen Chong;Mariolina Salio;Ian F. Hermans;Adrian L. Harris;Vincenzo Cerundolo - 通讯作者:
Vincenzo Cerundolo
Vincenzo Cerundolo的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Vincenzo Cerundolo', 18)}}的其他基金
MRC and DfID contribution to jointly funded rapid response strategic award
MRC 和 DfID 共同资助快速反应战略奖
- 批准号:
MC_PC_15002 - 财政年份:2015
- 资助金额:
$ 467.22万 - 项目类别:
Intramural
University Unit Award MRC Human Immunology Unit
大学单位奖 MRC 人类免疫学单位
- 批准号:
G1000800/1 - 财政年份:2010
- 资助金额:
$ 467.22万 - 项目类别:
Research Grant
Role of a Novel Scavenger Receptor in Epithelial Inflammatory Responses
新型清道夫受体在上皮炎症反应中的作用
- 批准号:
G0800158/1 - 财政年份:2008
- 资助金额:
$ 467.22万 - 项目类别:
Research Grant
A phase I trial in melanoma patients using dendritic cells pulsed with a novel synthetic iNKT cell agonist
使用新型合成 iNKT 细胞激动剂脉冲的树突状细胞对黑色素瘤患者进行的 I 期试验
- 批准号:
G0501975/1 - 财政年份:2006
- 资助金额:
$ 467.22万 - 项目类别:
Research Grant
相似国自然基金
Incentive and governance schenism study of corporate green washing behavior in China: Based on an integiated view of econfiguration of environmental authority and decoupling logic
- 批准号:
- 批准年份:2024
- 资助金额:万元
- 项目类别:外国学者研究基金项目
A study on prototype flexible multifunctional graphene foam-based sensing grid (柔性多功能石墨烯泡沫传感网格原型研究)
- 批准号:
- 批准年份:2020
- 资助金额:20 万元
- 项目类别:
相似海外基金
Phase Ib/II study of safety and efficacy of EZH2 inhibitor, tazemetostat, and PD-1 blockade for treatment of advanced non-small cell lung cancer
EZH2 抑制剂、他泽美司他和 PD-1 阻断治疗晚期非小细胞肺癌的安全性和有效性的 Ib/II 期研究
- 批准号:
10481965 - 财政年份:2024
- 资助金额:
$ 467.22万 - 项目类别:
Occupational exposure to ionizing radiation and the impacts on cancer incidence, and mortality: a record linkage cohort study of nearly one million workers in the Canadian National Dose Registry
电离辐射的职业暴露及其对癌症发病率和死亡率的影响:一项针对加拿大国家剂量登记处近百万工人的创纪录的连锁队列研究
- 批准号:
480070 - 财政年份:2023
- 资助金额:
$ 467.22万 - 项目类别:
Operating Grants
The role of diet, as mediated by the gut microbiome, on childhood arthritis disease activity: a feasibility intervention study.
肠道微生物组介导的饮食对儿童关节炎疾病活动的作用:一项可行性干预研究。
- 批准号:
489316 - 财政年份:2023
- 资助金额:
$ 467.22万 - 项目类别:
Operating Grants
The significance of new onset anxiety on health outcomes among women with cardiovascular disease: A Canadian Longitudinal Study of Aging cohort study
新发焦虑对患有心血管疾病的女性健康结果的重要性:加拿大老龄化纵向研究队列研究
- 批准号:
491767 - 财政年份:2023
- 资助金额:
$ 467.22万 - 项目类别:
Operating Grants
Caring for Providers to Improve Patient Experience (CPIPE) Study
关爱医疗服务提供者以改善患者体验 (CPIPE) 研究
- 批准号:
10556284 - 财政年份:2023
- 资助金额:
$ 467.22万 - 项目类别:
Development of a novel biomaterial model of collagen mediated genetic disease for study of collagen organisation and drug development
开发胶原蛋白介导的遗传病的新型生物材料模型,用于研究胶原蛋白组织和药物开发
- 批准号:
2897511 - 财政年份:2023
- 资助金额:
$ 467.22万 - 项目类别:
Studentship
Mechanistic Study of Inspiratory Training in Childhood Asthma
儿童哮喘吸气训练机制研究
- 批准号:
10637048 - 财政年份:2023
- 资助金额:
$ 467.22万 - 项目类别:
Sleep and Cardiometabolic Subgroup Discovery and Risk Prediction in United States Adolescents and Young Adults: A Multi-Study Multi-Domain Analysis of NHANES and NSRR
美国青少年和年轻人的睡眠和心脏代谢亚组发现和风险预测:NHANES 和 NSRR 的多研究多领域分析
- 批准号:
10639360 - 财政年份:2023
- 资助金额:
$ 467.22万 - 项目类别:
Impact of Medicaid Prescription Cap Policies on Treatment Outcomes for Opioid Use Disorder: A National Mixed Methods Study
医疗补助处方上限政策对阿片类药物使用障碍治疗结果的影响:一项国家混合方法研究
- 批准号:
10637024 - 财政年份:2023
- 资助金额:
$ 467.22万 - 项目类别:
Study of NEXMIF mosaic expression on neuronal development and connectivity in female mice
NEXMIF 镶嵌表达对雌性小鼠神经元发育和连接的影响研究
- 批准号:
10642436 - 财政年份:2023
- 资助金额:
$ 467.22万 - 项目类别: