HBV-specific T cell immunity in HBV/HIV coinfection
HBV/HIV 共感染中的 HBV 特异性 T 细胞免疫
基本信息
- 批准号:10771782
- 负责人:
- 金额:$ 73.84万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-07 至 2028-07-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAcute HepatitisAddressAdultAntiviral TherapyBiological Response ModifiersBiologyBloodBlood VolumeCD4 Lymphocyte CountCD4 Positive T LymphocytesCD8-Positive T-LymphocytesCD8B1 geneChronic HepatitisChronic Hepatitis BClinicalClinical TrialsCombined Modality TherapyDataDevelopmentDiseaseDisease ProgressionEnrollmentEvolutionExclusion CriteriaFine needle aspiration biopsyFlow CytometryFrequenciesFunctional disorderGenerationsHIVHIV InfectionsHeartHepatitis BHepatitis B InfectionHepatitis B Surface AntigensHepatitis B VirusImmuneImmune responseImmunityImmunologicsImmunologyImmunotherapyIn VitroInfectionInvestigationKnowledgeLiverLiver diseasesMediatingNational Institute of Allergy and Infectious DiseaseNewly DiagnosedOutcomeParticipantPatientsPeripheralPersonsPharmaceutical PreparationsPhenotypePoliciesPopulationPrimary carcinoma of the liver cellsRecoveryReportingResearchRoleSafetySamplingSiteSouthern AfricaT cell responseT-LymphocyteTestingTherapeuticTranslatingUnited States National Institutes of HealthViralVirus DiseasesZambiaantiretroviral therapyco-infectioncohorte Antigensexperienceinterestintrahepaticmortalitynovelnovel therapeuticsnucleoside analogperipheral bloodpreventprogramsresponseseroconversiontranscriptome sequencingviral DNAvirtual
项目摘要
Project Summary/Abstract
Among people living with HIV (PLWH), hepatitis B virus (HBV) is a common coinfection that contributes to high
rates of liver-related mortality. Even with early initiation of antiretroviral therapies that include HBV-active
nucleoside analogs (NA), mortality in people with HBV/HIV coinfection remains unacceptably high. There is a
strong rationale for additional HBV therapies for people with HBV/HIV infection. The HBV cure research agenda
is to (1) understand HBV biology, particularly the mechanisms that lead to HBV functional cure (FC), which is
defined as seroclearance of the hepatitis B surface antigen in blood, and (2) to evaluate novel antiviral and/or
immunotherapies that can increase HBV FC from its current rate of ~1% per year. However, at the present,
PLWH are poorly represented in HBV cure research, and HIV infection is an exclusion criterion in virtually all
clinical trials of novel HBV therapeutics. To accelerate the use of novel therapies in patients with HBV/HIV
coinfection, a better understanding is needed of host control of HBV in the setting of HIV. This project focuses
on cellular immune mechanisms of HBV control, particularly HBV-specific T cells. Our central hypothesis is that
in HBV/HIV coinfection, CD4 T cells represent a critical component of the immune response mediating HBV
control, including FC. This hypothesis will be tested through 3 specific aims. In Aim 1, we will investigate the
impact of HIV coinfection-associated immune dysregulation, especially CD4 depletion, on the quantity and
quality of HBV-specific T cell responses. In Aim 2, we will investigate the T-cell responses mediating HBV FC in
patients with HBV/HIV coinfection who are treated during inactive HBV infection (i.e., low HBV DNA, normal ALT,
no-minimal liver disease). In this group, we previously reported relatively high rates of HBV FC. In Aim 3, we will
characterize the evolution of HBV-specific T cell responses and the intrahepatic immune landscape during adult
acute HBV infection that typically results in HBV FC, with and without HIV coinfection. The above scientific
investigation will occur within a unique HBV clinical cohort in Zambia (Southern Africa), which includes adult
patients with chronic and acute HBV infection, with and without HIV coinfection, and features longitudinal large
volume blood and liver sampling before and during NA therapy. To date HBV FC has been ascertained >40
times in the cohort, mainly in participants with HBV/HIV coinfection. Successful completion of this project will
change the field by identifying immune mediators associated with HBV FC in HBV/HIV coinfection and by defining
specific immunological barriers to HBV FC in PLWH. It also will help to identify patient groups with coinfection
who may be more or less amenable to cure with emerging drugs based on their current or nadir CD4 and current
level of HBV control. In-depth analysis of specific CD4 T cells and the intrahepatic immune milieu will also be
highly significant in our understanding of chronic HBV infection without HIV.
项目总结/文摘
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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GEORG Michael LAUER其他文献
GEORG Michael LAUER的其他文献
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{{ truncateString('GEORG Michael LAUER', 18)}}的其他基金
Immune Control and Evadion during Acute HCV Infection
急性 HCV 感染期间的免疫控制和逃避
- 批准号:
9982171 - 财政年份:2016
- 资助金额:
$ 73.84万 - 项目类别:
CD4+ T Cells in Acute Versus Chronic HCV Infection
CD4 T 细胞在急性与慢性 HCV 感染中的作用
- 批准号:
8604683 - 财政年份:2013
- 资助金额:
$ 73.84万 - 项目类别:
CD4+ T Cells in Acute Versus Chronic HCV Infection
CD4 T 细胞在急性与慢性 HCV 感染中的作用
- 批准号:
8494258 - 财政年份:2013
- 资助金额:
$ 73.84万 - 项目类别:
CD4+ T Cells in Acute Versus Chronic HCV Infection
CD4 T 细胞在急性与慢性 HCV 感染中的作用
- 批准号:
8790390 - 财政年份:2013
- 资助金额:
$ 73.84万 - 项目类别:
CD4+ T Cells in Acute Versus Chronic HCV Infection
CD4 T 细胞在急性与慢性 HCV 感染中的作用
- 批准号:
9208086 - 财政年份:2013
- 资助金额:
$ 73.84万 - 项目类别:
Funtional T-cell Failure in Chronic HCV Infection
慢性 HCV 感染中的功能性 T 细胞衰竭
- 批准号:
8376117 - 财政年份:2012
- 资助金额:
$ 73.84万 - 项目类别:
Determinants of T-Cell mediated control in acute HCV Infection
T 细胞介导的急性 HCV 感染控制的决定因素
- 批准号:
7919779 - 财政年份:2010
- 资助金额:
$ 73.84万 - 项目类别:
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