Defining adaptive immune responses to Mtb-infection and TB disease among young children with and without HIV-exposure
定义接触或未接触 HIV 的幼儿对 Mtb 感染和结核病的适应性免疫反应
基本信息
- 批准号:10393701
- 负责人:
- 金额:$ 67.46万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-15 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdultAntibodiesB-LymphocytesBiological AssayBloodCD4 Positive T LymphocytesCD8-Positive T-LymphocytesChildChildhoodClinicalClinical ManagementContainmentCustomDevelopmentDiagnosticDiagnostic testsDiseaseEpidemiologyEpitopesExhibitsFlow CytometryHIVHIV InfectionsHIV/TBHealthHomeHouseholdImmuneImmune responseImmunityImmunologicsIndividualInfantInfectionKnowledgeLifeMonitorMorbidity - disease rateMothersMycobacterium tuberculosisPhenotypePneumoniaPrimary InfectionProspective cohortPulmonary TuberculosisSamplingT cell responseTuberculosisUgandaVaccinesWorkadaptive immune responsebasebiobankbiosignaturecytokinedesigndiagnostic toolexperienceglobal healthhigh riskhigh risk populationimprovedlatent infectionmortalitynovelnovel vaccinespre-clinicalreactivation from latencyresponsetuberculosis treatmentvaccine trial
项目摘要
PROJECT SUMMARY
Tuberculosis disease (TB), caused by Mycobacterium tuberculosis (Mtb) is a leading cause of morbidity and
mortality in young children <5 yr old. The vulnerability of young children to develop TB following primary infection
is not understood; this critical knowledge gap hampers efforts to develop a more effective vaccine and improved
diagnostic tests for this high-risk population. HIV-exposed (HEU) children are the majority of children living in the
homes of HIV+ adults, where they are more likely than HIV-unexposed-uninfected (HUU) children to be TB
exposed. Clinical, epidemiologic, and immunologic findings support that young, HEU children will exhibit
distinctive immune responses following Mtb-exposure; however, immune responses to Mtb-infection have not
been characterized in this high-risk population. Our proposal will comprehensively define adaptive immune
responses to Mtb-exposure and TB in children < 5yr using a pediatric TB household contact (HHC) study based
in Kampala, Uganda, where up to 20% of children are HEU. Our approach will identify unique immunologic
biosignatures driven by where the child sits on the TB disease spectrum, as well as by HIV-exposure status. We
hypothesize that immune biosignatures of Mtb-exposed asymptomatic HEU children will more closely resemble
those observed among children with TB, as compared to asymptomatic HUU children. If proven, this would
suggest that Mtb-exposed HEU children are more likely to be experiencing a pre-clinical rather than quiescent
or latent Mtb-infection. Such findings would have implications for the development of immune-based diagnostics
for Mtb-infection and TB disease that may perform differently in HIV-exposed and unexposed children, as well
as clinical management and monitoring of HEU-children following TB exposure. Working with a biorepository of
samples obtained from Ugandan children < 5 yr, and a proposed prospective cohort of Ugandan children < 5 yr
who are TB HHC, we will address three specific aims that: 1) define longitudinal, functional and phenotypic Mtb-
specific adaptive immune responses among young children who developed TB or remained asymptomatic; 2)
develop a pool of novel Mtb-epitopes and focused flow cytometry-based assay customized to detect Mtb-specific
T cell responses in young children; and 3) establish a unique Mtb-specific antibody Fc profile that defines children
with TB. Our proposal will advance pediatric global health by: 1) identification of immunologic signatures
reflecting successful containment of primary Mtb infection that can serve as correlates of protective immunity for
novel vaccine trials; 2) development of novel blood-based assays that discriminate between young children with
TB and those whom have been exposed but successfully contained their infection.
项目概要
结核病 (TB) 由结核分枝杆菌 (Mtb) 引起,是发病率和死亡率的主要原因
5岁以下幼儿的死亡率。幼儿在初次感染后易患结核病
不被理解;这一关键的知识差距阻碍了开发更有效的疫苗和改进疫苗的努力
针对这一高危人群的诊断测试。感染艾滋病毒(HEU)的儿童是生活在该地区的大多数儿童。
HIV 阳性成年人的家中,他们比未暴露于 HIV 的未感染 (HUU) 儿童更有可能患上结核病
裸露。临床、流行病学和免疫学研究结果表明,HEU 儿童将表现出
接触 Mtb 后出现独特的免疫反应;然而,对 Mtb 感染的免疫反应尚未
已在这一高危人群中得到了表征。我们的提案将全面定义适应性免疫
使用基于儿童结核病家庭接触 (HHC) 研究的 5 岁以下儿童对 Mtb 暴露和结核病的反应
在乌干达坎帕拉,高达 20% 的儿童使用高浓铀。我们的方法将识别独特的免疫学
生物特征由儿童在结核病谱上的位置以及艾滋病毒暴露状况驱动。我们
假设接触 Mtb 的无症状 HEU 儿童的免疫生物特征将更接近
与无症状 HUU 儿童相比,在结核病儿童中观察到的结果。如果被证明的话,这将
表明接触 Mtb 的 HEU 儿童更有可能经历临床前而非静止期
或潜伏性结核分枝杆菌感染。这些发现将对基于免疫的诊断的发展产生影响
结核分枝杆菌感染和结核病在暴露于艾滋病毒和未暴露于艾滋病毒的儿童中的表现也可能不同
作为结核病暴露后 HEU 儿童的临床管理和监测。使用生物样本库
从乌干达 5 岁以下儿童获得的样本,以及拟议的乌干达 5 岁以下儿童前瞻性队列
对于 TB HHC,我们将解决三个具体目标:1) 定义纵向、功能和表型 Mtb-
患有结核病或无症状的幼儿的特异性适应性免疫反应; 2)
开发一系列新型 Mtb 表位和基于流式细胞术的定制检测方法,用于检测 Mtb 特异性
幼儿的 T 细胞反应; 3) 建立定义儿童的独特 Mtb 特异性抗体 Fc 图谱
患有结核病。我们的提案将通过以下方式促进儿科全球健康:1)免疫特征识别
反映了原发性结核分枝杆菌感染的成功遏制,可以作为保护性免疫的相关因素
新型疫苗试验; 2)开发新的基于血液的检测方法来区分患有以下疾病的幼儿
结核病以及那些接触过但成功控制感染的人。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
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 }}
Christina Louise Lancioni其他文献
Christina Louise Lancioni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('Christina Louise Lancioni', 18)}}的其他基金
Defining adaptive immune responses to Mtb-infection and TB disease among young children with and without HIV-exposure
定义接触或未接触 HIV 的幼儿对 Mtb 感染和结核病的适应性免疫反应
- 批准号:
10253653 - 财政年份:2021
- 资助金额:
$ 67.46万 - 项目类别:
Defining adaptive immune responses to Mtb-infection and TB disease among young children with and without HIV-exposure
定义接触或未接触 HIV 的幼儿对 Mtb 感染和结核病的适应性免疫反应
- 批准号:
10591416 - 财政年份:2021
- 资助金额:
$ 67.46万 - 项目类别:
The impact of naltrexone treatment on opioid-induced immune and viral dysregulation during HIV-infection
纳曲酮治疗对 HIV 感染期间阿片类药物引起的免疫和病毒失调的影响
- 批准号:
10452590 - 财政年份:2018
- 资助金额:
$ 67.46万 - 项目类别:
The impact of naltrexone treatment on opioid-induced immune and viral dysregulation during HIV-infection
纳曲酮治疗对 HIV 感染期间阿片类药物引起的免疫和病毒失调的影响
- 批准号:
10212361 - 财政年份:2018
- 资助金额:
$ 67.46万 - 项目类别:
The impact of naltrexone treatment on opioid-induced immune and viral dysregulation during HIV-infection
纳曲酮治疗对 HIV 感染期间阿片类药物引起的免疫和病毒失调的影响
- 批准号:
9978796 - 财政年份:2018
- 资助金额:
$ 67.46万 - 项目类别:
The impact of naltrexone treatment on opioid-induced immune and viral dysregulation during HIV-infection
纳曲酮治疗对 HIV 感染期间阿片类药物引起的免疫和病毒失调的影响
- 批准号:
9788391 - 财政年份:2018
- 资助金额:
$ 67.46万 - 项目类别:
MTB directly regulates human CD4+ T cell activation
MTB 直接调节人类 CD4 T 细胞活化
- 批准号:
7708329 - 财政年份:2009
- 资助金额:
$ 67.46万 - 项目类别:
MTB directly regulates human CD4+ T cell activation
MTB 直接调节人类 CD4 T 细胞活化
- 批准号:
8234559 - 财政年份:2009
- 资助金额:
$ 67.46万 - 项目类别:
MTB directly regulates human CD4+ T cell activation
MTB 直接调节人类 CD4 T 细胞活化
- 批准号:
8102130 - 财政年份:2009
- 资助金额:
$ 67.46万 - 项目类别:
MTB directly regulates human CD4+ T cell activation
MTB 直接调节人类 CD4 T 细胞活化
- 批准号:
8515304 - 财政年份:2009
- 资助金额:
$ 67.46万 - 项目类别:
相似海外基金
Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
- 批准号:
MR/Z503605/1 - 财政年份:2024
- 资助金额:
$ 67.46万 - 项目类别:
Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
- 批准号:
2336167 - 财政年份:2024
- 资助金额:
$ 67.46万 - 项目类别:
Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
- 批准号:
2402691 - 财政年份:2024
- 资助金额:
$ 67.46万 - 项目类别:
Standard Grant
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
- 批准号:
2341428 - 财政年份:2024
- 资助金额:
$ 67.46万 - 项目类别:
Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
- 批准号:
24K12150 - 财政年份:2024
- 资助金额:
$ 67.46万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
- 批准号:
DE240100561 - 财政年份:2024
- 资助金额:
$ 67.46万 - 项目类别:
Discovery Early Career Researcher Award
RUI: Evaluation of Neurotrophic-Like properties of Spaetzle-Toll Signaling in the Developing and Adult Cricket CNS
RUI:评估发育中和成年蟋蟀中枢神经系统中 Spaetzle-Toll 信号传导的神经营养样特性
- 批准号:
2230829 - 财政年份:2023
- 资助金额:
$ 67.46万 - 项目类别:
Standard Grant
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
- 批准号:
23K09542 - 财政年份:2023
- 资助金额:
$ 67.46万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
- 批准号:
23K07552 - 财政年份:2023
- 资助金额:
$ 67.46万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
- 批准号:
23K07559 - 财政年份:2023
- 资助金额:
$ 67.46万 - 项目类别:
Grant-in-Aid for Scientific Research (C)