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Delaney AIDS Research Enterprise to Cure HIV

德莱尼艾滋病研究企业治愈艾滋病毒

基本信息

批准号：
9978687
负责人：
STEVEN Grant DEEKS
金额：
$ 554.5万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-14 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9978687
关键词：
Acquired Immunodeficiency Syndrome Adaptive Immune System Adult Affect Anti-Retroviral Agents B-Lymphocytes CD8-Positive T-Lymphocytes CTLA4 gene Cell physiology Cells Clinical Trials Collaborations Cytomegalovirus Disease Disease remission Effectiveness Effector Cell Future Generations Goals HIV HIV Infections HIV vaccine Helper-Inducer T-Lymphocyte Human IRF3 gene IRF4 gene Immune Immune response Immunity Immunologics Immunotherapeutic agent Individual Infection Infrastructure Interruption Intervention Laboratories Life Link Location Lymphoid Lymphoid Tissue Macaca Macaca mulatta Maintenance Malignant Neoplasms Measures Mediating Methods Mission Modeling Monkeys Nature Pathway interactions Phase I Clinical Trials Population Positron-Emission Tomography Radiolabeled Regimen Research Residual state Resources Rhesus Role SIV Safety Series System T cell response T-Lymphocyte Therapeutic Time Tissues Tracer Vaccinated Vaccines Viral Virus Work antiretroviral therapy base collaboratory combinatorial comparison intervention effector T cell imaging approach imaging modality immune checkpoint immune checkpoint blockade immune checkpoint blockers immune clearance immunogenicity improved industry partner inflammatory milieu meetings nonhuman primate novel vaccines programmed cell death protein 1 programs response therapy development vector vector vaccine virus characteristic

项目摘要

PROJECT SUMMARY/ABSTRACT The mission of the DARE Collaboratory is to harness the power of the adaptive immune system to reduce the size of the reservoir during antiretroviral therapy (ART) and to control any residual virus after ART is interrupted. Our overall hypothesis is that that durable remission of HIV infection will require a robust immune response that is persistent and functional. Moreover, these responses need to be in the right place at the right time. We propose four highly linked research foci aimed at reaching these goals. We will define the role of putative immune-privileged sanctuaries that enable SIV/HIV to persist during ART and use the monkey model to develop therapies to breach these sanctuaries (Initial Research Foci 1, IRF1). We will characterize the distribution on replication-competent virus in lymphoid tissues of ART-suppressed adults and develop PET imaging modalities to quantify this reservoir (IRF2). We will define the role of immune checkpoints (PD-1, others) and their blockade on T cell function in monkeys and people (IRF3). Finally, we will define the safety, immunogenicity, and anti-HIV effectiveness of a human CMV (HCMV) vectored HIV vaccine in HIV-infected adults on ART (IRF4). All four initial research foci are linked by their shared goal to understand how best to quantify, reduce, and control HIV in the human lymphoid system. We anticipate meeting the following milestones and deliverables: (1) definition of the replication-competent reservoir in lymphoid tissues from SIV- infected monkeys and HIV-infected humans on suppressive ART, (2) determination of whether B follicles serve as a immunologic sanctuary for infected CD4+ TFH and, if so, whether B follicular depletion reduces the size of the reservoir, (3) determination of the characteristics of virus-specific CD8+ T cell responses that have optimal activity for reservoir reduction and/or post-ART viral control, (4) determination if the tissue reservoir can be measured by radiolabeled tracers and PET scanning, (5) identification of the optimal combination of immune checkpoint blockers that enhance T-cell function and/or reverse HIV latency, (6) definition of the safety and immunogenicity of immune checkpoint blockers in treated SIV and HIV disease, (7) determination of the safety and immunogenicity of the HCMV/HIV vaccine in treated HIV disease, and (8) determination if B cell disruption and/or immune checkpoint blockade might be necessary for this vaccine (or other comparable interventions) to achieve reservoir reduction and/or durable remission. Our work will set the stage for a future proof-of-concept clinical trial of the HCMV/HIV vector in antiretroviral-treated individuals, either alone or in combination with B cell follicle disruption and/or immune checkpoint blockade.

项目总结/文摘

项目成果

期刊论文数量（26）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Microfluidic bead encapsulation above 20 kHz with triggered drop formation.

DOI：
10.1039/c8lc00514a
发表时间：
2018-12-07
期刊：
Lab on a chip
影响因子：
6.1
作者：
Clark IC;Abate AR
通讯作者：
Abate AR

Toll-like Receptor 7 Agonists in People Living With HIV: Implications for Immunotherapeutic Strategies for an HIV Cure.

HIV 感染者中的 Toll 样受体 7 激动剂：对 HIV 治愈免疫治疗策略的影响。

DOI：
10.1093/cid/ciaa1539
发表时间：
2021
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
0
作者：
Rasmussen,ThomasA;Lewin,SharonR
通讯作者：
Lewin,SharonR

GITR activation ex vivo impairs CD8 T cell function in people with HIV on antiretroviral therapy.

DOI：
10.1016/j.isci.2023.108165
发表时间：
2023-11-17
期刊：
ISCIENCE
影响因子：
5.8
作者：
Gubser, Celine;Pascoe, Rachel D.;Chang, Judy;Chiu, Chris;Solomon, Ajantha;Cao, Rosalyn;Rasmussen, Thomas A.;Lewin, Sharon R.
通讯作者：
Lewin, Sharon R.

Inducible HIV RNA transcription assays to measure HIV persistence: pros and cons of a compromise.

可诱导的HIV RNA转录测定法测量HIV持久性：妥协的利弊。

DOI：
10.1186/s12977-017-0385-y
发表时间：
2018-01-17
期刊：
Retrovirology
影响因子：
3.3
作者：
Plantin J;Massanella M;Chomont N
通讯作者：
Chomont N

The impact of immune checkpoint therapy on the latent reservoir in HIV-infected individuals with cancer on antiretroviral therapy.

DOI：
10.1097/qad.0000000000002919
发表时间：
2021-08-01
期刊：
AIDS (London, England)
影响因子：
0
作者：
Lau JSY;McMahon JH;Gubser C;Solomon A;Chiu CYH;Dantanarayana A;Chea S;Tennakoon S;Zerbato JM;Garlick J;Morcilla V;Palmer S;Lewin SR;Rasmussen TA
通讯作者：
Rasmussen TA