Correlates of protective immunity to HCV and rational vaccine design: Project 2
HCV 保护性免疫与合理疫苗设计的相关性:项目 2
基本信息
- 批准号:10608110
- 负责人:
- 金额:$ 79.13万
- 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:AccelerationAdoptionAffinityAntibodiesAntibody ResponseAntigensAntiviral AgentsAntiviral TherapyAttenuatedAutologousB cell differentiationB cell repertoireB-Lymphocyte SubsetsB-LymphocytesBiological AssayCD4 Positive T LymphocytesCanadaCell SeparationClinicalContractsDataDrug usageEgyptEpitopesEscape MutantExhibitsFlow CytometryGene Expression ProfileGenetic TranscriptionGlycoproteinsHelper-Inducer T-LymphocyteHepatitis CHepatitis C virusImmuneImmune responseImmunityImmunoglobulin-Secreting CellsIndividualInfectionInfection preventionInjecting drug userMediatingMemory B-LymphocyteMonoclonal AntibodiesMutationOutcomePeripheral Blood Mononuclear CellPhenotypePlasmaPlasma CellsPopulationPredispositionPrimary InfectionProliferatingPublic HealthResolutionSamplingSecondary toT memory cellVaccinationVaccine DesignVaccinesViralViral AntigensViremiaVirus Diseaseschronic infectioncohortexperiencelongitudinal analysisneutralizing antibodynew epidemicpolyclonal antibodypreventprogramsrecruitresponsesecondary infectionsingle-cell RNA sequencingstemtranscriptome sequencingvaccine strategy
项目摘要
Project 2. B Cell-Mediated Protection Against HCV Reinfection
Prevention of HCV infection remains an important public health objective even with the recent adoption of highly
effective antiviral therapies. A vaccine to prevent HCV persistence is needed to stem an emerging epidemic in
susceptible populations. Recall responses to secondary viral infections naturally emulate the protective immune
mechanisms associated with vaccination against viral antigens. Our findings suggest that spontaneous resolvers
may possess antigen-specific B cells that become readily activated by T follicular helper (Tfh) cells and expand
rapidly following HCV antigenic exposure. However, resolution of secondary HCV infection is low in individuals
cured of persistent HCV infection by DAAs, despite an initial burst of HCV-specific CD4+ T cells at the start of
DAA treatment. Such contrasting recall responses between these two scenarios implicate profound phenotypic
and functional differences in antigen-specific memory T and B cell responses between DAA-treated versus
untreated, resolving individuals.
We propose to elucidate the differences in antibody recall responses between individuals who spontaneously
resolve primary infection and subsequently either clear their secondary HCV reinfection (SR/SR) or develop
persistent infection (SR/CI). We will also compare these responses to those of DAA-treated individuals who are
cured of persistent HCV infection. We will analyze longitudinal samples from two separate cohorts of HCV
infected individuals for these studies. One cohort consists of people who inject drugs (PWIDs) recruited from
Montreal, Canada, who spontaneously resolve primary HCV infection but have different secondary reinfection
outcomes. The other cohort consists of individuals from Egypt who cleared persistent HCV infection following
DAA treatment (HCV-cured). We hypothesize that SR/SR PWID mount a more accelerated and sustained
memory B cell response that produces early, broadly neutralizing antibodies (bNAbs) that contribute to faster
clearance, while delayed antibody responses from SR/CI PWID or HCV-cured individuals fail to suppress viremia
early, facilitating viral escape from neutralization. We propose the following aims:
Aim 1. Determine the phenotypic and transcriptional profiles of bulk and antigen-specific memory B cells from
primary resolvers who were reinfected but experienced divergent infection sequelae.
Aim 2. Evaluate neutralizing efficacy and breadth of HCV-specific antibodies from resolvers with contrasting HCV
reinfection outcomes.
Aim 3. Determine phenotypic and functional changes in B cells of DAA-treated individuals before and after viral
clearance.
项目2. B细胞介导的抗HCV再感染保护作用
预防HCV感染仍然是一个重要的公共卫生目标,即使最近采用了高度
有效的抗病毒治疗。需要一种预防HCV持续存在的疫苗来阻止一种新的流行病,
易感人群。对继发性病毒感染的回忆反应自然地模仿保护性免疫
与针对病毒抗原的疫苗接种相关的机制。我们的研究结果表明,自发消退
可能具有抗原特异性B细胞,其容易被T滤泡辅助(Tfh)细胞激活并扩增
HCV抗原暴露后迅速死亡。然而,继发性HCV感染的解决是低的个人
通过DAA治愈了持续的HCV感染,尽管在治疗开始时HCV特异性CD 4 + T细胞的初始爆发,
DAA治疗。这两种情景之间的这种对比回忆反应暗示了深刻的表型
和抗原特异性记忆T和B细胞应答的功能差异,
未治疗的正在康复的患者
我们建议阐明抗体回忆反应的个体之间的差异,自发
解决原发性感染,随后清除继发性HCV再感染(SR/SR)或发展为
持续感染(SR/CI)。我们还将这些反应与DAA治疗的个体进行比较,
治愈持续性HCV感染。我们将分析两个独立的HCV队列的纵向样本,
受感染的人进行这些研究。一个队列由从以下地区招募的注射毒品者(PWID)组成:
蒙特利尔,加拿大,自发解决原发性HCV感染,但有不同的继发性再感染
结果。另一个队列由来自埃及的个体组成,这些个体在以下治疗后清除了持续性HCV感染。
DAA治疗(HCV治愈)。我们假设SR/SR PWID安装一个更加速和持续的
记忆B细胞反应,产生早期广泛中和抗体(bNAb),有助于更快地
清除,而来自SR/CI PWID或HCV治愈个体的延迟抗体应答不能抑制病毒血症
早期,促进病毒逃避中和。我们提出以下目标:
目标1。确定来自以下的本体和抗原特异性记忆B细胞的表型和转录谱:
再次感染但出现不同感染后遗症的原发性消退者。
目标2.评价与对照HCV的消退者中HCV特异性抗体的中和效力和广度
再感染结果。
目标3.确定病毒感染前后DAA处理个体的B细胞的表型和功能变化
间隙
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 }}
Arash Grakoui其他文献
Arash Grakoui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('Arash Grakoui', 18)}}的其他基金
Correlates of protective immunity to HCV and rational vaccine design
HCV 保护性免疫与合理疫苗设计的相关性
- 批准号:
10393614 - 财政年份:2021
- 资助金额:
$ 79.13万 - 项目类别:
Correlates of protective immunity to HCV and rational vaccine design: Admin Core
HCV 保护性免疫与合理疫苗设计的相关性:Admin Core
- 批准号:
10393615 - 财政年份:2021
- 资助金额:
$ 79.13万 - 项目类别:
Correlates of protective immunity to HCV and rational vaccine design
HCV 保护性免疫与合理疫苗设计的相关性
- 批准号:
10205764 - 财政年份:2021
- 资助金额:
$ 79.13万 - 项目类别:
Correlates of protective immunity to HCV and rational vaccine design: Project 2
HCV 保护性免疫与合理疫苗设计的相关性:项目 2
- 批准号:
10205768 - 财政年份:2021
- 资助金额:
$ 79.13万 - 项目类别:
Correlates of protective immunity to HCV and rational vaccine design: Project 2
HCV 保护性免疫与合理疫苗设计的相关性:项目 2
- 批准号:
10393618 - 财政年份:2021
- 资助金额:
$ 79.13万 - 项目类别:
Correlates of protective immunity to HCV and rational vaccine design
HCV 保护性免疫与合理疫苗设计的相关性
- 批准号:
10608105 - 财政年份:2021
- 资助金额:
$ 79.13万 - 项目类别:
Correlates of protective immunity to HCV and rational vaccine design: Admin Core
HCV 保护性免疫与合理疫苗设计的相关性:Admin Core
- 批准号:
10205765 - 财政年份:2021
- 资助金额:
$ 79.13万 - 项目类别:
Correlates of protective immunity to HCV and rational vaccine design: Admin Core
HCV 保护性免疫与合理疫苗设计的相关性:Admin Core
- 批准号:
10608106 - 财政年份:2021
- 资助金额:
$ 79.13万 - 项目类别:
Dynamics of antigen specific B and Tfh responses during acute and chronic HCV
急性和慢性 HCV 期间抗原特异性 B 和 Tfh 反应的动态
- 批准号:
10063938 - 财政年份:2017
- 资助金额:
$ 79.13万 - 项目类别:
Dynamics of antigen specific B and Tfh responses during acute and chronic HCV
急性和慢性 HCV 期间抗原特异性 B 和 Tfh 反应的动态
- 批准号:
10305612 - 财政年份:2017
- 资助金额:
$ 79.13万 - 项目类别:
相似海外基金
Investigating the Adoption, Actual Usage, and Outcomes of Enterprise Collaboration Systems in Remote Work Settings.
调查远程工作环境中企业协作系统的采用、实际使用和结果。
- 批准号:
24K16436 - 财政年份:2024
- 资助金额:
$ 79.13万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
WELL-CALF: optimising accuracy for commercial adoption
WELL-CALF:优化商业采用的准确性
- 批准号:
10093543 - 财政年份:2024
- 资助金额:
$ 79.13万 - 项目类别:
Collaborative R&D
Unraveling the Dynamics of International Accounting: Exploring the Impact of IFRS Adoption on Firms' Financial Reporting and Business Strategies
揭示国际会计的动态:探索采用 IFRS 对公司财务报告和业务战略的影响
- 批准号:
24K16488 - 财政年份:2024
- 资助金额:
$ 79.13万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 79.13万 - 项目类别:
EU-Funded
Assessing the Coordination of Electric Vehicle Adoption on Urban Energy Transition: A Geospatial Machine Learning Framework
评估电动汽车采用对城市能源转型的协调:地理空间机器学习框架
- 批准号:
24K20973 - 财政年份:2024
- 资助金额:
$ 79.13万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 79.13万 - 项目类别:
EU-Funded
De-Adoption Beta-Blockers in patients with stable ischemic heart disease without REduced LV ejection fraction, ongoing Ischemia, or Arrhythmias: a randomized Trial with blinded Endpoints (ABbreviate)
在没有左心室射血分数降低、持续性缺血或心律失常的稳定型缺血性心脏病患者中停用β受体阻滞剂:一项盲法终点随机试验(ABbreviate)
- 批准号:
481560 - 财政年份:2023
- 资助金额:
$ 79.13万 - 项目类别:
Operating Grants
Our focus for this project is accelerating the development and adoption of resource efficient solutions like fashion rental through technological advancement, addressing longer in use and reuse
我们该项目的重点是通过技术进步加快时装租赁等资源高效解决方案的开发和采用,解决更长的使用和重复使用问题
- 批准号:
10075502 - 财政年份:2023
- 资助金额:
$ 79.13万 - 项目类别:
Grant for R&D
Engage2innovate – Enhancing security solution design, adoption and impact through effective engagement and social innovation (E2i)
Engage2innovate — 通过有效参与和社会创新增强安全解决方案的设计、采用和影响 (E2i)
- 批准号:
10089082 - 财政年份:2023
- 资助金额:
$ 79.13万 - 项目类别:
EU-Funded
Collaborative Research: SCIPE: CyberInfrastructure Professionals InnoVating and brOadening the adoption of advanced Technologies (CI PIVOT)
合作研究:SCIPE:网络基础设施专业人员创新和扩大先进技术的采用 (CI PIVOT)
- 批准号:
2321091 - 财政年份:2023
- 资助金额:
$ 79.13万 - 项目类别:
Standard Grant