Project #1 Bar and Shaw
项目
基本信息
- 批准号:10224007
- 负责人:
- 金额:$ 35.97万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-08-01 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAntibodiesAntibody ResponseArchivesAutologousBar CodesBiologicalCellsCharacteristicsClinical TrialsDiscriminationEtiologyFutureGenerationsGeneticGoalsGrowthHIVHIV-1HumanImmune responseImmunityImmunologicsImmunotherapeutic agentImmunotherapyIndividualInfectionInterruptionKineticsLeadMacacaMacaca mulattaMeasuresMediatingModelingMolecular ConformationMonoclonal AntibodiesPathogenicityPatternPlasmaPrevention therapyPropertyResistanceRestRoleSIVT cell responseT memory cellTestingTherapeuticTissuesVariantViralViral reservoirViremiaVirusVirus Replicationcell typeclinical developmentclinical efficacyclinical outcome measuresdesignexhaustionexperimental studyimmunoregulationimproved functioningnovelnovel strategiespre-clinicalpreclinical studypreventreactivation from latencysimian human immunodeficiency virustherapeutic evaluationviral rebound
项目摘要
The current generation of broadly neutralizing HIV-specific monoclonal antibodies (bNAbs) have many
exciting applications in HIV-1 prevention, therapy, and cure. Therapeutic administration of bNAbs in HIVinfected
individuals is being pursued with the overlapping goals of maintaining plasma virus suppression,
enabling Fc-mediated clearance of virus-infected cells, and enhancing host immune responses. Preclinical
studies of single and combination bNAbs in simian-human immunodeficiency virus (SHIV)-infected macaques
have demonstrated remarkably potent and durable virus suppression, augmentation of anti-HIV immune
responses, and possible reductions of the cellular reservoir. In contrast, recent human clinical trials have
shown markedly less potency and durability, no effect on the cellular reservoir, and frequent pre-existent and
emergent bNAb-resistant variants. The discordant results of pre-clinical SHIV/macaque experiments and
human clinical trials highlight several fundamental questions underlying bNAb immunotherapy and the need for
a well-characterized SHIV/macaque model of HIV latency in which to study them.
Project 1 will capitalize on two recent advances in NHP models to elucidate the determinants of TF
SHIV rebound from bNAb immunotherapy: (i) our group’s discovery of a novel strategy to create pathogenic
SHIVs that retain the antigenic conformation of transmitted/founder (TF) HIV-1 Env and the viral kinetics and
persistence properties of primary HIV-1 strains, and (ii) a strategy to place silent genetic tags, or barcodes,
within a virus stock, which allows for discrimination of each viral lineage and enables sophisticated modeling of
viral kinetics, reactivation and rebound. A central premise of this project is that a well-characterized
barcoded-TF SHIV model of latency and virus reactivation will enable delineation of the determinants of viral
rebound and elucidate the capabilities, mechanisms, and immunomodulatory effects of bNAb administration.
Utilizing this novel TF SHIV model, we will test combination bNAb immunotherapy in the context of
treatment interruption after early and late ART initiation and in viremia. Specific Aims of Project 1 are to: 1)
determine how bnAb immunotherapy alters virus reactivation, tissues of origin and subsequent virus growth; 2)
identify the etiology and impact of neutralization resistance; 3) determine whether treatment interruption or
bNAb immunotherapy change the size of the latent reservoir; and 4) determine how bNAbs modulate host
antibody and T cell responses. Results from these studies will elucidate the viral kinetics and immunologic
characteristics of latency and viral rebound in a novel, biologically relevant TF SHIV model that could facilitate
broad testing of therapeutic and eradicative strategies. Further, the determination of bNAb immunotherapy’s
clinical efficacy, mechanisms of bNAb mediated virus suppression, effects on the archived viral reservoir, and
impact on host immune responses will inform the design of future bNAb immunotherapeutic strategies for virus
suppression and eradication.
当前一代广泛中和的hiv特异性单克隆抗体(bNAbs)有许多
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 }}
Katharine June Bar其他文献
Katharine June Bar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('Katharine June Bar', 18)}}的其他基金
Determining the effects of broadly neutralizing antibodies at antiretroviral therapy initiation
确定广泛中和抗体在抗逆转录病毒治疗开始时的作用
- 批准号:
10772448 - 财政年份:2023
- 资助金额:
$ 35.97万 - 项目类别:
Complementing broadly neutralizing antibodies and autologous responses to restrict virus escape and durably suppress HIV-1
补充广泛中和抗体和自体反应,以限制病毒逃逸并持久抑制 HIV-1
- 批准号:
10469169 - 财政年份:2022
- 资助金额:
$ 35.97万 - 项目类别:
Complementing broadly neutralizing antibodies and autologous responses to restrict virus escape and durably suppress HIV-1
补充广泛中和抗体和自体反应,以限制病毒逃逸并持久抑制 HIV-1
- 批准号:
10608215 - 财政年份:2022
- 资助金额:
$ 35.97万 - 项目类别:
Characterizing the viral and host effector mechanisms that govern HIV-1 rebound
表征控制 HIV-1 反弹的病毒和宿主效应机制
- 批准号:
10629260 - 财政年份:2021
- 资助金额:
$ 35.97万 - 项目类别:
Characterizing the viral and host effector mechanisms that govern HIV-1 rebound
表征控制 HIV-1 反弹的病毒和宿主效应机制
- 批准号:
10437036 - 财政年份:2021
- 资助金额:
$ 35.97万 - 项目类别:
Novel macrophage-tropic transmitted/founder SHIV model of CNS persistence to evaluate CRISPR/Cas9 gene editing
用于评估 CRISPR/Cas9 基因编辑的新型巨噬细胞嗜性传播/中枢神经系统持久性 SHIV 模型
- 批准号:
10331568 - 财政年份:2021
- 资助金额:
$ 35.97万 - 项目类别:
Novel macrophage-tropic transmitted/founder SHIV model of CNS persistence to evaluate CRISPR/Cas9 gene editing
用于评估 CRISPR/Cas9 基因编辑的新型巨噬细胞嗜性传播/中枢神经系统持久性 SHIV 模型
- 批准号:
10443900 - 财政年份:2021
- 资助金额:
$ 35.97万 - 项目类别:
Novel macrophage-tropic transmitted/founder SHIV model of CNS persistence to evaluate CRISPR/Cas9 gene editing
用于评估 CRISPR/Cas9 基因编辑的新型巨噬细胞嗜性传播/中枢神经系统持久性 SHIV 模型
- 批准号:
10606618 - 财政年份:2021
- 资助金额:
$ 35.97万 - 项目类别:
Characterizing the viral and host effector mechanisms that govern HIV-1 rebound
表征控制 HIV-1 反弹的病毒和宿主效应机制
- 批准号:
10332623 - 财政年份:2021
- 资助金额:
$ 35.97万 - 项目类别:
Immunological Strategies to Modulate SIV Rebound Following ART Interruption
ART 中断后调节 SIV 反弹的免疫策略
- 批准号:
10224003 - 财政年份:2017
- 资助金额:
$ 35.97万 - 项目类别:
相似海外基金
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 35.97万 - 项目类别:
Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 35.97万 - 项目类别:
Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 35.97万 - 项目类别:
Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 35.97万 - 项目类别:
Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 35.97万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 35.97万 - 项目类别:
Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 35.97万 - 项目类别:
Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 35.97万 - 项目类别:
Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
- 批准号:
23K00129 - 财政年份:2023
- 资助金额:
$ 35.97万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
- 批准号:
2883985 - 财政年份:2023
- 资助金额:
$ 35.97万 - 项目类别:
Studentship