Immune correlates of LTBI in HIV-exposed infants
HIV 暴露婴儿 LTBI 的免疫相关性
基本信息
- 批准号:10543401
- 负责人:
- 金额:$ 57.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-01-05 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAgeAge YearsAntibodiesAntigensAreaBCG LiveBCG VaccineBacille Calmette-Guerin vaccinationBindingBiological AssayBiological MarkersBirthBloodBreast FeedingCD4 Positive T LymphocytesCD8-Positive T-LymphocytesCell MaturationCellsCessation of lifeCharacteristicsChildChildhoodClinicalClinical TrialsCollaborationsColorCountryCytometryDataData AnalysesDevelopmentDiagnosisDiagnostic testsDiseaseEnrollmentExerciseFlow CytometryGene Expression ProfileGenesGoldHIVHIV InfectionsHIV-exposed uninfected infantHelper-Inducer T-LymphocyteIL17 geneImmuneImmune checkpoint inhibitorImmune responseImmunityImmunoglobulin AImmunoglobulin GImmunoglobulin MImmunologic MemoryImmunologic TestsImmunologicsImmunologyIncidenceIndividualInfantInfant DevelopmentInfant MortalityInfectionIntakeInterferonsInterleukin-2International Maternal Pediatric Adolescent AIDS Clinical TrialsLaboratoriesLifeLiteratureLongevityMaternally-Acquired ImmunityMeasuresMediatingMemoryMeningeal TuberculosisMiliary TuberculosisMothersMycobacterium bovisMycobacterium tuberculosisMycobacterium tuberculosis antigensNewborn InfantParticipantPeripheralPeripheral Blood Mononuclear CellPersonsPharmaceutical PreparationsPhenotypePlasmaPopulationPostpartum PeriodPregnancyPregnant WomenPrevalencePrevention therapyPreventive therapyProliferatingProtocols documentationPulmonary TuberculosisRegulatory T-LymphocyteResearchResearch PersonnelRiskRisk FactorsRoleSamplingSerologySortingSystemT-Lymphocyte SubsetsTNF geneTNFSF5 geneTestingTimeTranscriptTubeTuberculosisTuberculosis VaccinesVaccinesWomanWorkantenatalbiophysical techniquescytokinedata exchangehigh riskimprovedin uteroindexinginterleukin-21interleukin-22isoniazidmemory CD4 T lymphocytemonocytemortality riskmycobacterialnew technologypregnantpreventprogrammed cell death protein 1progression riskprotein purificationreactivation from latencyrepositoryresponsesafety assessmentsafety testingsingle-cell RNA sequencingtranscriptometranscriptomicstuberculosis immunityvaccine responsevaccine strategy
项目摘要
Almost
whom
leading
of
vaccine,
acquiring
to
preponderance
PBMC
aimed
HIV+ pregnant
(interferon
Among
1a
pregnancy
show
phenotypic
CFP-10
maternal
serology
maternal
transferred
data
first
compared
using
cytometry
understanding
women
uncover
2 billion of the world's population has latent Mycobacterium tuberculosis (Mtb) infection (LTBI) of
approximately 10% progress to active TB disease. TB disease is a major cause of infant mortality,
to 240,000 childhood deaths in 2015. The risk of death from TB is 3 times higher in children <5 yrs.
age compared to older children. Although much effort is being exercised to develop an effective TB
BCG is still the only approved TB vaccine. Despite BCG vaccination, infants have a high risk of
new TB infections (TBI) and for progression of LTBI to active TB disease. Literature on immunity
in HIV exposed uninfected infants is inconclusive. role of a Th2 bias and
of regulatory T cells (T regs) also need consideration. For this proposal, we have access to
and plasma of maternal-infant samples from a completed IMPAACT trial (P1078). This study was
to test the safety of Isoniazid preventative therapy (IPT) during pregnancy or post-partum in
women who were followed until I year post-partum. Incidence of LTBI was tested by IGRA
gamma release assay). Approximately 30% of the women were IGRA positive at study entry.
infants, approximately 5.6% were IGRA + at 12 weeks and remained positive at 44 weeks. In Aim
we will test the hypotheses that HIV exposed uninfected (HEU) infants whose mothers have LTBI during
are sensitized to mycobacterial antigens in utero, develop immunologic memory to Mtb and
an altered response to BCG vaccination . For this aim we will perform detailed analyses of CD4 T cell
subsets as well as antigen specific intra-cellular cytokine memory response to RD-1 antigens
and ESAT-6, a DosR latency antigen and to PPD by flow cytometry. In Aim 2 we hypothesize that
factors such as Ab to Mtb can influence the infant immune response . For this aim a systems
approach for biophysical and functional characterization of FcR binding Ab will be performed in
plasma at delivery and infant plasma at weeks 12 and 44, for ascertaining longevity of passively
maternal Ab. Cytokine profile, country of origin, and IPT during pregnancy will be included in
analysis of maternal-infant immunity. In Aim 3 we hypothesize that infants diagnosed with LTBI in the
year of life have distinct gene transcriptomic profiles in monocytes and antigen specific CD4+ T cells
to those who are not infected with TB . In this aim we will profile CD4 T cells and monocytes
single cell transcriptomics. Transcriptional profiles will be correlated with immunologic profile by flow
and Ab profile by systems serology described in Aims 1 and 2 These studies are relevant for
immunological mechanisms of maternal-infant interaction in the context of LTBI in HIV+
and their EUI, and impact on BCG vaccine responses. Importantly they have the potential to
sensitive biomarkers of LTBI and yield information relevant for vaccine strategies.
BCG
vaccine The
956
.
差不多了
他是谁
领先
的
疫苗,
获取
至
优势
PBMC
瞄准
HIV+孕妇
(干扰素
其中
1A
妊娠
显示
表型
CFP-10
母性
血清学
母性
已转接
数据
第一
比较
使用
细胞计数法
理解
女人
揭开面纱
世界上有20亿人口患有潜在的结核分枝杆菌感染(LTBI)
活动性结核病的进展约为10%。结核病是婴儿死亡的主要原因,
2015年儿童死亡人数降至24万人。5岁儿童死于结核病的风险是前者的3倍。
与年龄较大的孩子相比。尽管正在努力开发一种有效的结核病
卡介苗仍然是唯一被批准的结核病疫苗。尽管接种了卡介苗,但婴儿患BCG的风险很高
新的结核病感染(TBI)和LTBI向活动性结核病的进展。关于免疫的文献
在暴露于艾滋病毒的未感染婴儿中,这一点尚不确定。Th2偏向的作用和
调节性T细胞(T Regs)的数量也需要考虑。对于此提案,我们可以访问
和来自完成的IMPAACT试验的母婴样本的血浆(P1078)。这项研究是
为了测试异烟肼预防治疗(IPT)在孕期或产后的安全性
一直被跟踪到产后一年的女性。用IGRA对LTBI的发生率进行检验
伽马释放试验)。在研究开始时,大约30%的女性IGRA呈阳性。
婴儿中,12周时IGRA阳性的约5.6%,44周时仍为阳性。在AIM
我们将检验这样的假设,即母亲在LTBI期间接触艾滋病毒的未感染(HEU)婴儿
在子宫中对分枝杆菌抗原敏感,对结核分枝杆菌和结核分枝杆菌产生免疫记忆
对卡介苗接种的不同反应。为此,我们将对CD4T细胞进行详细的分析
RD-1抗原的亚群及抗原特异性细胞内细胞因子记忆反应
流式细胞仪检测DosR潜伏期抗原ESAT-6与PPD的结合。在目标2中,我们假设
抗结核分枝杆菌抗体等因素可影响婴儿的免疫应答。为此目的,一种系统
将在#年进行FCR结合抗体的生物物理和功能表征方法
分娩时血浆和12周和44周婴儿血浆,以确定被动的寿命
母体抗体。细胞因子概况、原产国和怀孕期间的IPT将包括在
母婴免疫状况分析。在目标3中,我们假设被诊断为LTBI的婴儿在
生命年份在单核细胞和抗原特异的CD4+T细胞中有不同的基因转录图谱
给那些没有感染结核病的人。在这个目标中,我们将分析CD4T细胞和单核细胞
单细胞转录学。转录图谱将通过Flow与免疫学图谱相关联
以及AIMS 1和AIMS 2中所述的系统血清学分析。这些研究与
HIV+LTBI背景下母婴相互作用的免疫学机制
以及它们的EUI,以及对卡介苗疫苗反应的影响。重要的是,他们有可能
LTBI的敏感生物标志物和与疫苗策略相关的产量信息。
卡介苗
疫苗
九百五十六
。
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 }}
Savita Pahwa其他文献
Savita Pahwa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('Savita Pahwa', 18)}}的其他基金
Immunity and HIV persistence in perinatal HIV infection
围产期 HIV 感染中的免疫和 HIV 持续性
- 批准号:
9211649 - 财政年份:2016
- 资助金额:
$ 57.57万 - 项目类别:
Immunity and HIV persistence in perinatal HIV infection
围产期 HIV 感染中的免疫和 HIV 持续性
- 批准号:
9302666 - 财政年份:2016
- 资助金额:
$ 57.57万 - 项目类别:
Antibody Responses in Aging SIV Infected Monkeys
感染 SIV 的衰老猴子的抗体反应
- 批准号:
9120783 - 财政年份:2015
- 资助金额:
$ 57.57万 - 项目类别:
Immune Activation in Virologically Suppressed Indian HIV-infected Patients
病毒学受到抑制的印度艾滋病毒感染者的免疫激活
- 批准号:
8540075 - 财政年份:2013
- 资助金额:
$ 57.57万 - 项目类别:
Immune Activation in Virologically Suppressed Indian HIV-infected Patients
病毒学受到抑制的印度艾滋病毒感染者的免疫激活
- 批准号:
8728729 - 财政年份:2013
- 资助金额:
$ 57.57万 - 项目类别:
相似国自然基金
靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
- 批准号:JCZRQN202500010
- 批准年份:2025
- 资助金额:0.0 万元
- 项目类别:省市级项目
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
- 批准号:2025JJ70209
- 批准年份:2025
- 资助金额:0.0 万元
- 项目类别:省市级项目
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
- 批准号:
- 批准年份:2024
- 资助金额:0 万元
- 项目类别:面上项目
甜茶抑制AGE-RAGE通路增强突触可塑性改善小鼠抑郁样行为
- 批准号:2023JJ50274
- 批准年份:2023
- 资助金额:0.0 万元
- 项目类别:省市级项目
蒙药额尔敦-乌日勒基础方调控AGE-RAGE信号通路改善术后认知功能障碍研究
- 批准号:
- 批准年份:2022
- 资助金额:33 万元
- 项目类别:地区科学基金项目
补肾健脾祛瘀方调控AGE/RAGE信号通路在再生障碍性贫血骨髓间充质干细胞功能受损的作用与机制研究
- 批准号:
- 批准年份:2022
- 资助金额:52 万元
- 项目类别:面上项目
LncRNA GAS5在2型糖尿病动脉粥样硬化中对AGE-RAGE 信号通路上相关基因的调控作用及机制研究
- 批准号:n/a
- 批准年份:2022
- 资助金额:10.0 万元
- 项目类别:省市级项目
围绕GLP1-Arginine-AGE/RAGE轴构建探针组学方法探索大柴胡汤异病同治的效应机制
- 批准号:81973577
- 批准年份:2019
- 资助金额:55.0 万元
- 项目类别:面上项目
AGE/RAGE通路microRNA编码基因多态性与2型糖尿病并发冠心病的关联研究
- 批准号:81602908
- 批准年份:2016
- 资助金额:18.0 万元
- 项目类别:青年科学基金项目
高血糖激活滑膜AGE-RAGE-PKC轴致骨关节炎易感的机制研究
- 批准号:81501928
- 批准年份:2015
- 资助金额:18.0 万元
- 项目类别:青年科学基金项目
相似海外基金
Collaborative Research: Resolving the LGM ventilation age conundrum: New radiocarbon records from high sedimentation rate sites in the deep western Pacific
合作研究:解决LGM通风年龄难题:西太平洋深部高沉降率地点的新放射性碳记录
- 批准号:
2341426 - 财政年份:2024
- 资助金额:
$ 57.57万 - 项目类别:
Continuing Grant
Collaborative Research: Resolving the LGM ventilation age conundrum: New radiocarbon records from high sedimentation rate sites in the deep western Pacific
合作研究:解决LGM通风年龄难题:西太平洋深部高沉降率地点的新放射性碳记录
- 批准号:
2341424 - 财政年份:2024
- 资助金额:
$ 57.57万 - 项目类别:
Continuing Grant
PROTEMO: Emotional Dynamics Of Protective Policies In An Age Of Insecurity
PROTEMO:不安全时代保护政策的情绪动态
- 批准号:
10108433 - 财政年份:2024
- 资助金额:
$ 57.57万 - 项目类别:
EU-Funded
The role of dietary and blood proteins in the prevention and development of major age-related diseases
膳食和血液蛋白在预防和发展主要与年龄相关的疾病中的作用
- 批准号:
MR/X032809/1 - 财政年份:2024
- 资助金额:
$ 57.57万 - 项目类别:
Fellowship
Atomic Anxiety in the New Nuclear Age: How Can Arms Control and Disarmament Reduce the Risk of Nuclear War?
新核时代的原子焦虑:军控与裁军如何降低核战争风险?
- 批准号:
MR/X034690/1 - 财政年份:2024
- 资助金额:
$ 57.57万 - 项目类别:
Fellowship
Walkability and health-related quality of life in Age-Friendly Cities (AFCs) across Japan and the Asia-Pacific
日本和亚太地区老年友好城市 (AFC) 的步行适宜性和与健康相关的生活质量
- 批准号:
24K13490 - 财政年份:2024
- 资助金额:
$ 57.57万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Discovering the (R)Evolution of EurAsian Steppe Metallurgy: Social and environmental impact of the Bronze Age steppes metal-driven economy
发现欧亚草原冶金的(R)演变:青铜时代草原金属驱动型经济的社会和环境影响
- 批准号:
EP/Z00022X/1 - 财政年份:2024
- 资助金额:
$ 57.57万 - 项目类别:
Research Grant
ICF: Neutrophils and cellular senescence: A vicious circle promoting age-related disease.
ICF:中性粒细胞和细胞衰老:促进与年龄相关疾病的恶性循环。
- 批准号:
MR/Y003365/1 - 财政年份:2024
- 资助金额:
$ 57.57万 - 项目类别:
Research Grant
Doctoral Dissertation Research: Effects of age of acquisition in emerging sign languages
博士论文研究:新兴手语习得年龄的影响
- 批准号:
2335955 - 财政年份:2024
- 资助金额:
$ 57.57万 - 项目类别:
Standard Grant
Shaping Competition in the Digital Age (SCiDA) - Principles, tools and institutions of digital regulation in the UK, Germany and the EU
塑造数字时代的竞争 (SCiDA) - 英国、德国和欧盟的数字监管原则、工具和机构
- 批准号:
AH/Y007549/1 - 财政年份:2024
- 资助金额:
$ 57.57万 - 项目类别:
Research Grant