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

基本信息

  • 批准号:
    10772448
  • 负责人:
  • 金额:
    $ 88.03万
  • 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:
    2023-08-17 至 2027-07-31
  • 项目状态:
    未结题

项目摘要

Project Summary ART initiation (ARTi) is a unique clinical juncture in which virus replication and host immune responses are in flux and treatment of a substantial component of people living with HIV (PLWH) is possible. In both preclinical studies and recent clinical trials, infusion of broadly neutralizing antibodies (bnAbs) at ARTi has shown exciting preliminary results, but key questions about the mechanisms of action, the requisite bnAb properties, and the extent of clinical impact remain. Further, it is unclear if these benefits can be extended to the >35 million PLWH currently on suppressive ART, by using bnAbs after treatment interruption and ART re-initiation. Several clinical trials are planned or ongoing, but the complexity of human research limit the ability to definitively elucidate key mechanisms. Our scientific premise is that our molecularly defined, mixed bnAb-sensitive and resistant, barcoded transmitted/founder (TF) SHIV/NHP model system is uniquely poised to determine the extent and durability of bnAb activity at ARTi/re-initiation and decipher the mechanistic role of neutralization potency and effector function on reservoir dynamics, durable immune responses, and virus control. Our group has generated a body of work demonstrating that TF SHIVs reproduce key features of HIV-1 immunopathogenesis. We have expanded the model to incorporate genetic barcoding and virus inocula containing defined mixtures of bnAb-sensitive and resistant viruses. In this system, each animal is infected with a precise ratio of TF SHIVs encoding wildtype (WT; bnAb-sensitive) and escape mutant (EM; bnAb resistant) viruses, which have similar replication kinetics but markedly different sensitivities to V3-glycan bnAbs. Because WT and EM viruses have unique barcodes, we can track bnAb-sensitive vs. resistant virus clonotypes over time and across tissues through high-throughput sequencing, allowing for statistically powerful within-animal comparisons, as well as comparisons across treatment arms. Here, we will leverage this novel NHP system to determine the effects of bnAbs at ARTi and re-initiation and dissect the roles of bnAbs’ neutralizing and effector functions through a coordinated NHP experiment comparing 4 treatment groups: (i) ART alone, (ii) ART + bnAb, (iii) ART + bnAb with disabled effector function, and (iv) ART + bnAb with enhanced effector function. We will then determine if similar effects can be seen with use of bnAbs at ART re-initiation in animals already on suppressive ART who underwent ATI. This strategy allows us to define bnAb’s clinical impact and test our overall hypothesis that both the neutralizing potency and effector function of bnAbs at ARTi are essential to activity on the reservoir, host immunity, and induction of virus control. Successful completion of this project would have substantial significance to the HIV cure field, as it rigorously tests promising roles for bnAbs in HIV cure strategies that could guide the clinical development of bnAbs in cure strategies.
项目总结

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

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:
    $ 88.03万
  • 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:
    $ 88.03万
  • 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:
    $ 88.03万
  • 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:
    $ 88.03万
  • 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:
    $ 88.03万
  • 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:
    $ 88.03万
  • 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:
    $ 88.03万
  • 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:
    $ 88.03万
  • 项目类别:
Project #1 Bar and Shaw
项目
  • 批准号:
    10224007
  • 财政年份:
    2017
  • 资助金额:
    $ 88.03万
  • 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:
    $ 88.03万
  • 项目类别:

相似海外基金

Life outside institutions: histories of mental health aftercare 1900 - 1960
机构外的生活:1900 - 1960 年心理健康善后护理的历史
  • 批准号:
    DP240100640
  • 财政年份:
    2024
  • 资助金额:
    $ 88.03万
  • 项目类别:
    Discovery Projects
Development of a program to promote psychological independence support in the aftercare of children's homes
制定一项计划,促进儿童之家善后护理中的心理独立支持
  • 批准号:
    23K01889
  • 财政年份:
    2023
  • 资助金额:
    $ 88.03万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Integrating Smoking Cessation in Tattoo Aftercare
将戒烟融入纹身后护理中
  • 批准号:
    10452217
  • 财政年份:
    2022
  • 资助金额:
    $ 88.03万
  • 项目类别:
Integrating Smoking Cessation in Tattoo Aftercare
将戒烟融入纹身后护理中
  • 批准号:
    10670838
  • 财政年份:
    2022
  • 资助金额:
    $ 88.03万
  • 项目类别:
Aftercare for young people: A sociological study of resource opportunities
年轻人的善后护理:资源机会的社会学研究
  • 批准号:
    DP200100492
  • 财政年份:
    2020
  • 资助金额:
    $ 88.03万
  • 项目类别:
    Discovery Projects
Creating a National Aftercare Strategy for Survivors of Pediatric Cancer
为小儿癌症幸存者制定国家善后护理策略
  • 批准号:
    407264
  • 财政年份:
    2019
  • 资助金额:
    $ 88.03万
  • 项目类别:
    Operating Grants
Aftercare of green infrastructure: creating algorithm for resolving human-bird conflicts
绿色基础设施的善后工作:创建解决人鸟冲突的算法
  • 批准号:
    18K18240
  • 财政年份:
    2018
  • 资助金额:
    $ 88.03万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Development of an aftercare model for children who have experienced invasive procedures
为经历过侵入性手术的儿童开发善后护理模型
  • 批准号:
    17K12379
  • 财政年份:
    2017
  • 资助金额:
    $ 88.03万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Development of a Comprehensive Aftercare Program for children's self-reliance support facility
为儿童自力更生支持设施制定综合善后护理计划
  • 批准号:
    17K13937
  • 财政年份:
    2017
  • 资助金额:
    $ 88.03万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Project#2 Extending Treatment Effects Through an Adaptive Aftercare Intervention
项目
  • 批准号:
    8742767
  • 财政年份:
    2014
  • 资助金额:
    $ 88.03万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了