Correlates of protective immunity to HCV and rational vaccine design: Project 1
HCV 保护性免疫与合理疫苗设计的相关性:项目 1
基本信息
- 批准号:10205767
- 负责人:
- 金额:$ 19.25万
- 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:AftercareAntibody ResponseAntiviral AgentsAntiviral TherapyB-LymphocytesBenchmarkingBiological AssayBloodCD4 Positive T LymphocytesCD8-Positive T-LymphocytesCanadaCellsChemicalsChronicChronic Hepatitis CChronic PhaseCoculture TechniquesCountryDefectDeveloping CountriesDevelopmentEgyptExhibitsExposure toFlow CytometryGoalsHepatitis CHepatitis C PrevalenceHepatitis C virusHigh PrevalenceImmuneImmune responseImmunityImmunologic FactorsIndividualInfectionInjecting drug userInterferon Type IIKineticsKnowledgeLeukocytesLiverLiver diseasesMaintenanceMeasuresMediatingMediator of activation proteinModelingMolecular ProfilingNorth AmericaPan GenusPathway interactionsPatientsPhase II Clinical TrialsPhenotypeProductionPublic HealthQuantitative Reverse Transcriptase PCRRNARecoveryResolutionRiskRoleSamplingSourceStainsT cell responseT memory cellT-Cell ProliferationT-LymphocyteT-cell receptor repertoireTarget PopulationsTechnologyTimeVaccinationVaccine DesignVaccinesViralViruscohortcytokineenzyme linked immunospot assayfunctional genomicsimmune functionimmunogenicitymarginalized populationmemory CD4 T lymphocyteneutralizing antibodynovel vaccinesopioid epidemicpandemic diseasepublic health prioritiesreconstitutionresponsesingle-cell RNA sequencingvaccine candidate
项目摘要
Project 1: High resolution profiling of protective HCV-specific CD4 T cells
Abstract
Hepatitis C virus (HCV) is a virus that infects the liver and is transmitted through contaminated blood. HCV
infection is still a public health priority and a major cause of liver disease worldwide, especially in developing
countries like Egypt. New HCV infections are also on the rise in North America in association with the opioid
epidemic. While new antiviral drugs can cure >95% of infected individuals, many do not know that they are
infected and remain at risk of developing liver disease and an active source of new infections. Furthermore,
successful treatment does not prevent reinfection if the individual is re-exposed to the virus. Hence, there is an
urgent need for vaccines that can protect against this virus. Unfortunately, despite our knowledge about the
immune response against HCV, we still do not have an effective vaccine. Recent results from the only vaccine
candidate that made it into a large scale (Phase 2) clinical trial did not show any protection in people who inject
drugs (PWID) at risk of HCV infection. This means that we need to understand better the immune factors and
cells that protect against HCV in cohorts of patients who are able to clear the virus spontaneously. The
overarching goal of this proposal t is to define these factors that are essential to achieve protective immunity.
The aim of this specific project (Project 1) is to characterize the role and functions of a subset of white blood
cells known as helper CD4 lymphocytes in a group of PWID who are constantly being exposed to the virus where
some are able to clear it several times and others that cannot. We will identify the differences in those who clear
the virus repeatedly and those who cannot. We will also compare the immune response in individuals who clear
the virus spontaneously versus those who clear it post treatment to determine if they are less protected against
HCV if they are re-exposed to it. We will use two unique cohorts of subjects, a PWID cohort from Montreal,
Canada and a cohort of subjects undergoing antiviral therapy from Egypt, the country with the highest prevalence
of HCV. The results obtained in this project will be complementary to Project 2 that will examine the antibody
response to HCV in the same subjects. We will use the latest technology to examine the immune response at
the functional and genomic level and identify cellular pathways and key molecules that are implicated in the
development and maintenance of a protective immune response. We will attempt to use chemical compounds
to correct the defects observed in those who are unable to clear the virus. Such compounds may be combined
with different vaccine candidates, as described in project 3, to enhance their immunogenicity and protective
capacity.
项目1:保护性HCV特异性CD4 T细胞的高分辨率分析
抽象的
丙型肝炎病毒(HCV)是一种感染肝脏并通过污染的血液传播的病毒。 HCV
感染仍然是公共卫生的优先事项,也是全球肝病的主要原因,尤其是在发展
像埃及这样的国家。与阿片类药物联合的新型HCV感染也在增加
流行性。虽然新的抗病毒药可以治愈> 95%的感染者,但许多人不知道他们是
感染并仍然有患肝病的风险和新感染的积极来源。此外,
如果个人重新暴露于病毒,则成功的治疗不会阻止再感染。因此,有一个
迫切需要可以防止这种病毒的疫苗。不幸的是,尽管我们知道
对HCV的免疫反应,我们仍然没有有效的疫苗。唯一疫苗的最新结果
将其分为大规模(第2阶段)临床试验的候选人没有显示注射的人的任何保护
有HCV感染风险的药物(PWID)。这意味着我们需要更好地了解免疫因素和
能够自发清除病毒的患者同类中HCV的细胞。这
该提案的总体目标是定义这些因素对于获得保护性免疫必不可少的因素。
该特定项目的目的(项目1)是表征白血部分的作用和功能
一组PWID中称为辅助CD4淋巴细胞的细胞,他们不断暴露于病毒中
有些人能够多次清除,而另一些则无法清除。我们将确定那些清除的人的差异
该病毒反复和那些无法的人。我们还将比较清除的个人的免疫反应
该病毒是自发的,与那些在治疗后清除IT的人确定它们是否受到较少保护
如果HCV重新暴露于其。我们将使用两个独特的人群,一个来自蒙特利尔的PWID队列,
加拿大和一系列受试者从埃及接受抗病毒疗法,该国的患病率最高
HCV。该项目中获得的结果将与项目2进行补充,该项目将检查抗体
对同一主题中HCV的反应。我们将使用最新技术检查免疫反应
功能和基因组水平,并鉴定与涉及的细胞途径和关键分子
保护和维护保护性免疫反应。我们将尝试使用化合物
纠正无法清除病毒的人中观察到的缺陷。这样的化合物可以组合
如项目3中所述,使用不同的候选疫苗,以增强其免疫原性和保护性
容量。
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 }}
NAGLAA H. SHOUKRY其他文献
NAGLAA H. SHOUKRY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('NAGLAA H. SHOUKRY', 18)}}的其他基金
Correlates of protective immunity to HCV and rational vaccine design: Clinical Core
HCV 保护性免疫与合理疫苗设计的相关性:临床核心
- 批准号:
10393616 - 财政年份:2021
- 资助金额:
$ 19.25万 - 项目类别:
Correlates of protective immunity to HCV and rational vaccine design: Clinical Core
HCV 保护性免疫与合理疫苗设计的相关性:临床核心
- 批准号:
10205766 - 财政年份:2021
- 资助金额:
$ 19.25万 - 项目类别:
Correlates of protective immunity to HCV and rational vaccine design: Clinical Core
HCV 保护性免疫与合理疫苗设计的相关性:临床核心
- 批准号:
10608107 - 财政年份:2021
- 资助金额:
$ 19.25万 - 项目类别:
Correlates of protective immunity to HCV and rational vaccine design: Project 1
HCV 保护性免疫与合理疫苗设计的相关性:项目 1
- 批准号:
10608109 - 财政年份:2021
- 资助金额:
$ 19.25万 - 项目类别:
Correlates of protective immunity to HCV and rational vaccine design: Project 1
HCV 保护性免疫与合理疫苗设计的相关性:项目 1
- 批准号:
10393617 - 财政年份:2021
- 资助金额:
$ 19.25万 - 项目类别:
相似国自然基金
B7H4-LILRB4信号调控B细胞代谢重编程机制在同种抗体产生及防治AMR中的作用
- 批准号:82371792
- 批准年份:2023
- 资助金额:49.00 万元
- 项目类别:面上项目
抗变构/单体形式的C反应蛋白关键抗原表位199-206抗体在狼疮性肾炎小管间质病变中的作用机制及其靶向治疗研究
- 批准号:82300829
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
TSC1对滤泡辅助性T细胞在抗体介导的排斥反应中的调控作用及其机制研究
- 批准号:82370760
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
NK细胞靶向微泡超声分子成像评价抗体介导排斥反应的研究
- 批准号:82302225
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
抗BP180抗体活化基底层角质形成细胞中Fn14-TRAF2-ZFP36轴促进大疱性类天疱疮炎症反应的机制探究
- 批准号:82373476
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
相似海外基金
First-in-human study of a potent anti-HBsAg neutralizing antibody
强效抗 HBsAg 中和抗体的首次人体研究
- 批准号:
10550458 - 财政年份:2023
- 资助金额:
$ 19.25万 - 项目类别:
Treatment of Inflammatory Complications of Viral Pneumonia
病毒性肺炎炎症并发症的治疗
- 批准号:
10383991 - 财政年份:2022
- 资助金额:
$ 19.25万 - 项目类别:
A Randomized Controlled Trial of Prophylaxis with Direct-acting Antivirals for Kidney Transplantation from Hepatitis C virus-infected donor to Uninfected Recipients (PREVENT-HCV)
直接作用抗病毒药物预防丙型肝炎病毒感染供者肾移植至未感染受者的随机对照试验 (PREVENT-HCV)
- 批准号:
10597168 - 财政年份:2022
- 资助金额:
$ 19.25万 - 项目类别:
A Randomized Controlled Trial of Prophylaxis with Direct-acting Antivirals for Kidney Transplantation from Hepatitis C virus-infected donor to Uninfected Recipients (PREVENT-HCV)
直接作用抗病毒药物预防丙型肝炎病毒感染供者肾移植至未感染受者的随机对照试验 (PREVENT-HCV)
- 批准号:
10405358 - 财政年份:2022
- 资助金额:
$ 19.25万 - 项目类别:
COVID-19 comorbidity studies in Syrian hamster models
叙利亚仓鼠模型中的 COVID-19 合并症研究
- 批准号:
10450889 - 财政年份:2021
- 资助金额:
$ 19.25万 - 项目类别: