Project 2: Analysis of Reservoir Dynamics in SIV-Infected Rhesus Macaques
项目 2:感染 SIV 的恒河猴的储库动力学分析
基本信息
- 批准号:10459662
- 负责人:
- 金额:$ 40.12万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-04-01 至 2027-03-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAftercareApoptosisBiological AssayBloodBlood CirculationCD4 Positive T LymphocytesCD8B1 geneCellsDNAEpitopesFrequenciesGene ExpressionGenomicsHIV-1HumanImmuneIndividualInfectionLymphoid TissueMacacaMacaca mulattaMeasurementMediatingModelingMutationNaturePathogenesisPeripheralPhasePlasmaPopulationPopulation AnalysisPreventionProcessPropertyResearch PersonnelResistanceRestSIVShapesSpleenTestingTimeVaccine TherapyViralViral GenesViral reservoirViremiaVirusantibody-dependent cell cytotoxicitycell typedesignexperimental studyinsightlymph nodesneutralizing antibodynonhuman primatenovelsimian human immunodeficiency virusviral rebound
项目摘要
Summary – Project 2
Non-human primate (NHP) models have provided valuable insights into HIV-1 pathogenesis, prevention, and
treatment. Of particular importance are models involving infection of rhesus macaques with SIV or SHIV. With
respect to viral reservoirs, we have previously shown that widespread SIV dissemination and reservoir seeding
take place in the first few days of infection. The Barouch lab have also explored cure strategies in rhesus
macaques, focusing on immune stimulating agents, therapeutic vaccination, broadly neutralizing antibodies, and
combinations of these approaches. These studies have provided some promising early evidence of effects on
viral rebound and post-treatment control. The Siliciano lab provided early evidence that latently infected resting
CD4+ T cells in blood, lymph nodes, and spleen are an important reservoir in SIV-infected macaques. Available
studies on reservoir dynamics in SIV-infected macaques suggest an overall similarity to reservoir dynamics in
PLWH. In the studies proposed here, we will capitalize on the advantages of NHP models to explore the
establishment, composition, and dynamics of the latent reservoir. The studies are designed to extend the studies
in PLWH proposed in Project 1 and address critical questions in reservoir dynamics that cannot be easily
addressed in humans. The Specific Aims of this project are:
Specific Aim 1. To define the cell types responsible for the first and second phases of decay of viremia
following initiation of ART. We hypothesize (1) that most of the plasma virus is produced by a rapidly decaying
population of activated CD4+ T cells present in the lymph nodes and other lymphoid tissues, (2) that the 2nd
phase of decay reflects the elimination of a distinct population of CD4+ T cells in a lower state of activation that
produce virus for a longer period of time, and (3) that the 2nd phase represents selection process that shapes
the composition and dynamics of the stable latent reservoir.
Specific Aim 2. To determine the mechanism by which infected cells are eliminated during the first and
second phases of decay. Using CD8 depletion experiments, we will test the hypothesis that the elimination of
2nd phase cells is mediated by virus-specific CTL.
摘要-项目二
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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Dan H. Barouch其他文献
Pharmacokinetic interaction assessment of an HIV broadly neutralizing monoclonal antibody VRC07-523LS: a cross-protocol analysis of three phase 1 trials in people without HIV
- DOI:
10.1186/s12865-025-00687-7 - 发表时间:
2025-02-19 - 期刊:
- 影响因子:2.700
- 作者:
Tariro D. Chawana;Stephen R. Walsh;Lynda Stranix-Chibanda;Zvavahera M. Chirenje;Chenchen Yu;Lily Zhang;Kelly E. Seaton;Jack Heptinstall;Lu Zhang;Carmen A. Paez;Theresa Gamble;Shelly T. Karuna;Philip Andrew;Brett Hanscom;Magdalena E. Sobieszczyk;Srilatha Edupuganti;Cynthia L. Gay;Sharon B. Mannheimer;Christopher B. Hurt;Kathryn E. Stephenson;Laura L. Polakowski;Hans Spiegel;Margaret Yacovone;Stephanie Regenold;Catherine Yen;Jane AG. Baumblatt;Lucio Gama;Dan H. Barouch;Estelle Piwowar-Manning;Richard A. Koup;Georgia D. Tomaras;Ollivier Hyrien;Alison C. Roxby;Yunda Huang - 通讯作者:
Yunda Huang
On-patient medical record and mRNA therapeutics using intradermal microneedles
住院病历与使用皮内微针的信使核糖核酸疗法
- DOI:
10.1038/s41563-024-02115-4 - 发表时间:
2025-02-24 - 期刊:
- 影响因子:38.500
- 作者:
Jooli Han;Maria Kanelli;Yang Liu;John L. Daristotle;Apurva Pardeshi;Timothy A. Forster;Ari Karchin;Brandon Folk;Lukas Murmann;Lisa H. Tostanoski;Sebastian E. Carrasco;Shahad K. Alsaiari;Erika Yan Wang;Khanh Tran;Linzixuan Zhang;Behnaz Eshaghi;Lauren Levy;Sydney Pyon;Charles Sloane;Stacey Qiaohui Lin;Alicia Lau;Collin F. Perkinson;Moungi G. Bawendi;Dan H. Barouch;Frédo Durand;Robert Langer;Ana Jaklenec - 通讯作者:
Ana Jaklenec
Attenuated emMycobacterium tuberculosis/em vaccine protection in a low-dose murine challenge model
减毒鼠伤寒沙门菌疫苗在低剂量小鼠攻击模型中的保护作用
- DOI:
10.1016/j.isci.2023.106963 - 发表时间:
2023-06-16 - 期刊:
- 影响因子:4.100
- 作者:
Samuel J. Vidal;Daniel Sellers;Jingyou Yu;Shoko Wakabayashi;Jaimie Sixsmith;Malika Aid;Julia Barrett;Sage F. Stevens;Xiaowen Liu;Wenjun Li;Courtney R. Plumlee;Kevin B. Urdahl;Amanda J. Martinot;Dan H. Barouch - 通讯作者:
Dan H. Barouch
SIV proviruses seeded later in infection are harbored in short-lived CD4sup+/sup T cells
在感染后期植入的猴免疫缺陷病毒(SIV)前病毒存在于短寿命的CD4<sup>+</sup>T细胞中
- DOI:
10.1016/j.celrep.2025.115663 - 发表时间:
2025-05-27 - 期刊:
- 影响因子:6.900
- 作者:
Narmada Sambaturu;Emily J. Fray;Vivek Hariharan;Fengting Wu;Carolin Zitzmann;Francesco R. Simonetti;Dan H. Barouch;Janet D. Siliciano;Robert F. Siliciano;Ruy M. Ribeiro;Alan S. Perelson;Carmen Molina-París;Thomas Leitner - 通讯作者:
Thomas Leitner
Nonhuman primate antigenic cartography of SARS-CoV-2
非人类灵长类动物对 SARS-CoV-2 的抗原图谱
- DOI:
10.1016/j.celrep.2024.115140 - 发表时间:
2025-01-28 - 期刊:
- 影响因子:6.900
- 作者:
Annika Rössler;Antonia Netzl;Ninaad Lasrado;Jayeshbhai Chaudhari;Barbara Mühlemann;Samuel H. Wilks;Janine Kimpel;Derek J. Smith;Dan H. Barouch - 通讯作者:
Dan H. Barouch
Dan H. Barouch的其他文献
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{{ truncateString('Dan H. Barouch', 18)}}的其他基金
Multi-Omics Analysis of Broadly Neutralizing Antibodies and Therapeutic Vaccination
广泛中和抗体和治疗性疫苗的多组学分析
- 批准号:
10724219 - 财政年份:2023
- 资助金额:
$ 40.12万 - 项目类别:
Multi-Omics Correlates of Broadly Neutralizing Antibody Efficacy
广泛中和抗体功效的多组学关联
- 批准号:
10724224 - 财政年份:2023
- 资助金额:
$ 40.12万 - 项目类别:
CoVPN LOC Cross-Protocol Infrastructure Supplement for GY15 and GY16
适用于 GY15 和 GY16 的 CoVPN LOC 跨协议基础设施补充
- 批准号:
10571201 - 财政年份:2022
- 资助金额:
$ 40.12万 - 项目类别:
Project 2: Analysis of Reservoir Dynamics in SIV-Infected Rhesus Macaques
项目 2:感染 SIV 的恒河猴的储库动力学分析
- 批准号:
10599365 - 财政年份:2022
- 资助金额:
$ 40.12万 - 项目类别:
HIV Vaccines Clinical Trials Network Leadership and Operations Center
HIV 疫苗临床试验网络领导和运营中心
- 批准号:
10311601 - 财政年份:2021
- 资助金额:
$ 40.12万 - 项目类别:
CoVPN 3005 - Efficacy, Immunogenicity, and Safety of SARS-CoV-2 Recombinant Protein Vaccine with Adjuvant in Adults 18 Years of Age and Older
CoVPN 3005 - SARS-CoV-2 重组蛋白疫苗与佐剂对 18 岁及以上成人的功效、免疫原性和安全性
- 批准号:
10415762 - 财政年份:2021
- 资助金额:
$ 40.12万 - 项目类别:
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