Characterization of neutralizing antitoxins and epitopes in Clostridium difficile patients
艰难梭菌患者中和抗毒素和表位的特征
基本信息
- 批准号:10549285
- 负责人:
- 金额:$ 38.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-01-16 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:AntibodiesAntibody ResponseB-LymphocytesBindingBiological MarkersCellsCharacteristicsClinicalClostridium difficileDataDevelopmentDiagnosisDiseaseDisease OutbreaksDisease OutcomeDisease ProgressionEnzyme-Linked Immunosorbent AssayEpitopesFinancial costFrequenciesFutureGoalsHumanImmuneImmune responseImmunityImmunodominant EpitopesImmunoglobulin AImmunoglobulin GImmunoglobulin IsotypesIndividualInfectionKineticsKnowledgeMapsMediatingMonoclonal AntibodiesMorbidity - disease rateOutcomePassive ImmunotherapyPatientsPreventionPropertyRecurrenceSerumSeveritiesSeverity of illnessSpecificityTestingTherapeuticToxinVaccinesVirulence Factorsantitoxindesigngut inflammationindividual patientinfection managementintestinal injurymethod developmentmortalityneutralizing antibodynovelnovel vaccinesoutcome predictionpredictive markerpredictive testresponsetool
项目摘要
Abstract
Intestinal injury and inflammation in Clostridium difficile infection (CDI), an increasing cause of morbidity,
mortality and financial cost in the US, is mediated by two large clostridial toxins: TcdA & TcdB. Although
antibodies against each toxin have been shown to be associated with protection, it is unclear what types of
antibodies and their epitopes are responsible for effective immunity against CDI in patients. The goal of this
project is to define the characteristics of a protective humoral immune response in CDI and the major
neutralizing TcdA & TcdB epitopes. The hypothesis is that host antibodies directed against major neutralizing
epitopes in TcdA & TcdB confer protection against CDI. To test this hypothesis, we will first validate our
preliminary finding on neutralizing anti-TcdA/TcdB responses that correlate protection against severe CDI will
also correlate protection against recurrence (Aim 1); subsequently we will characterize C. difficile toxin-specific
B cell responses at clonal level and correlate these with CDI disease progression and recurrence (Aim 2); and
finally we will clone neutralizing antibodies from individual B cells to obtain a representative panel of human
protective monoclonal antibodies against the two toxins and characterize their binding epitopes and reactivity
to a variety of toxins produced by major C. difficile endemic and outbreak strains (Aim 3). The completion of
these specific aims can lead to the discovery of antibody biomarkers that predict outcomes of the most
significant clinical issues in CDI management, including CDI occurrence, severity, and recurrence.
Identification and characterization of protective antibodies may also facilitate the development of novel passive
immunotherapy and vaccine approaches.
摘要
艰难梭菌感染(CDI)中的肠道损伤和炎症是发病率增加的原因,
死亡率和经济成本,是由两个大的梭菌毒素介导的:TcdA和TcdB。虽然
针对每种毒素的抗体已被证明与保护有关,但尚不清楚哪种类型的抗体具有保护作用。
抗体和它们的表位负责患者中针对CDI的有效免疫。这个目标
项目是确定CDI中保护性体液免疫应答的特征,
中和TcdA和TcdB表位。假设是针对主要中和抗体的宿主抗体
TcdA和TcdB中的表位赋予针对CDI的保护。为了验证这一假设,我们将首先验证我们的
关于中和抗TcdA/TcdB应答的初步发现,
也与防止复发相关(目标1);随后我们将描述C。艰难梭菌毒素特异性
克隆水平的B细胞应答,并将这些应答与CDI疾病进展和复发相关联(目的2);以及
最后,我们将从单个B细胞中克隆中和抗体,以获得一组代表性的人类
针对这两种毒素的保护性单克隆抗体,并表征其结合表位和反应性
产生的各种毒素。difficile地方性和爆发性菌株(Aim 3)。完成
这些特定的目标可以导致抗体生物标志物的发现,这些生物标志物可以预测大多数疾病的结果。
CDI管理中的重大临床问题,包括CDI发生率、严重程度和复发。
保护性抗体的鉴定和表征也可以促进新型被动免疫的开发。
免疫疗法和疫苗方法。
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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Hanping Feng其他文献
Hanping Feng的其他文献
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{{ truncateString('Hanping Feng', 18)}}的其他基金
Preventing norovirus and Clostridium difficile gastroenteritis by engineered probiotic yeast Saccharomyces boulardii secreting multi-specific single-domain antibodies
通过分泌多特异性单域抗体的工程益生菌布拉酵母菌预防诺如病毒和艰难梭菌胃肠炎
- 批准号:
10540345 - 财政年份:2020
- 资助金额:
$ 38.63万 - 项目类别:
Preventing norovirus and Clostridium difficile gastroenteritis by engineered probiotic yeast Saccharomyces boulardii secreting multi-specific single-domain antibodies
通过分泌多特异性单域抗体的工程益生菌布拉酵母菌预防诺如病毒和艰难梭菌胃肠炎
- 批准号:
10320907 - 财政年份:2020
- 资助金额:
$ 38.63万 - 项目类别:
Characterization of neutralizing antitoxins and epitopes in Clostridium difficile patients
艰难梭菌患者中和抗毒素和表位的特征
- 批准号:
10319522 - 财政年份:2020
- 资助金额:
$ 38.63万 - 项目类别:
Probiotic yeast secreting single-domain antibodies to prevent Clostridium difficile and Campylobacter jejuni disease
益生菌酵母分泌单域抗体来预防艰难梭菌和空肠弯曲菌疾病
- 批准号:
10364713 - 财政年份:2019
- 资助金额:
$ 38.63万 - 项目类别:
Probiotic yeast secreting single-domain antibodies to prevent Clostridium difficile and Campylobacter jejuni disease
益生菌酵母分泌单域抗体来预防艰难梭菌和空肠弯曲菌疾病
- 批准号:
10584482 - 财政年份:2019
- 资助金额:
$ 38.63万 - 项目类别:
A Novel Humanized Tetra-specific Antibody against Clostridium difficile Infection
一种抗艰难梭菌感染的新型人源化四特异性抗体
- 批准号:
10432036 - 财政年份:2017
- 资助金额:
$ 38.63万 - 项目类别:
A Novel Humanized Tetra-specific Antibody against Clostridium difficile Infection
一种抗艰难梭菌感染的新型人源化四特异性抗体
- 批准号:
9362547 - 财政年份:2017
- 资助金额:
$ 38.63万 - 项目类别:
Toxemia and systemic disease in Clostridium difficile infection
艰难梭菌感染的毒血症和全身性疾病
- 批准号:
8664002 - 财政年份:2013
- 资助金额:
$ 38.63万 - 项目类别:
Epithelium, dendritic cells, and Clostridium difficile associated colitis
上皮、树突状细胞和艰难梭菌相关结肠炎
- 批准号:
7887611 - 财政年份:2010
- 资助金额:
$ 38.63万 - 项目类别:
Development of Vaccines against Clostridium difficile Infection
艰难梭菌感染疫苗的研制
- 批准号:
7903007 - 财政年份:2010
- 资助金额:
$ 38.63万 - 项目类别:
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