Pediatric Adolescent Virus Elimination (PAVE) Martin Delaney Collaboratory

儿科青少年病毒消除 (PAVE) Martin Delaney 合作实验室

基本信息

批准号：
10620823
负责人：
Ann M Chahroudi
金额：
$ 590.41万
依托单位：
JOHNS HOPKINS UNIVERSITY
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：
2021-08-16 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10620823
关键词：
15 year old Acceleration Active Immunization Address Adherence Adolescent Adolescent and Young Adult Adult Aftercare Age Antibody Therapy Award Binding Biological Markers Biological Models Biology Characteristics Child Childhood Clinical Clinical Research Clinical Trials Collaborations Communities Country Data Development Disease remission Epidemic Epigenetic Process Ethics Evolution Exhibits Faculty Feedback Fostering Future Gender Generations Goals HIV HIV-1 Human Image Immune Immune Targeting Immune system Immunity Immunization Immunologic Markers Immunologics Immunotherapeutic agent Industry Infant Infection International Interruption Intervention Intervention Trial Investigation Knowledge Leadership Life Measures Mediating Mission Modeling Monitor Myeloid Cells Oregon Passive Immunization Perinatal Infection Plasma Population Pre-Clinical Model Predisposition Prevention Primates Research Research Personnel Resources Rest Role Safety Sampling Science Shock Structure T cell response T-Lymphocyte Testing Therapeutic Time Vertical Disease Transmission Viral Viral reservoir Virus Vision Work Youth aged antiretroviral therapy career development cohort collaboratory combat community engagement cost efficacy clinical trial efficacy evaluation imaging modality industry partner infant infection insight latent HIV reservoir literacy meetings memory CD4 T lymphocyte multidisciplinary neutralizing antibody novel novel strategies novel therapeutics pediatric human immunodeficiency virus perinatal HIV pre-clinical preclinical efficacy preclinical safety preclinical study programs purge response side effect social stigma synergism technology platform therapy duration viral rebound young adult

项目摘要

ABSTRACT The immediate establishment of the latent HIV-1 reservoir in resting memory CD4+ T cells precludes HIV-1 cure, compelling ART for a lifetime in children. The mission of the PAVE Collaboratory is to use cutting-edge science to establish a deep and broad understanding of the immunopathogenesis of pediatric HIV-1 reservoirs, across the age spectrum, and to demonstrate preclinical safety and efficacy of novel therapeutics to eradicate reservoirs and control rebound that will pave the way for future interventional human studies toward a lifetime of sustained HIV-1 control off ART. We hypothesize that the unique features of the infant immune system at the time of reservoir establishment impact the characteristics of long-term virus persistence, susceptibility to immune- mediated clearance, and reactivation that are distinct from adult infections, warranting in-depth investigation to inform cure therapeutics suitable for children. We will test this hypothesis and execute the PAVE Scientific Agenda through accomplishment of the following Specific Aims: 1. Define the establishment and evolution of the HIV latent reservoir in perinatal infection. 2. Enhance pediatric immunity and broadly neutralizing antibody (bNAb) delivery to achieve post-treatment control of HIV-1 off ART. 3. Deploy immune-targeted strategies to eliminate virus reservoirs. 4. Optimize virologic, immunologic, and imaging methods to assess efficacy of HIV-1/S(H)IV cure interventions. 5. Foster community engagement in pediatric HIV cure research. The PAVE program is multidisciplinary, multicultural, and iterative with a nimble structure encompassed by four highly synergistic Research Foci and a domestic and international community program that will rapidly incorporate new scientific directions and feedback from our stakeholders. The PAVE leadership team spans diverse scientific expertise and exhibits additional diversity in terms of gender, academic rank, and country of origin. Each of the Research Foci also includes junior faculty co-Investigators to facilitate their career development within the HIV-1 research space. Through the collective efforts of our scientific leadership, Executive Committee, Scientific Advisory Board, investigators, industry partners, network collaborations, and domestic and international community program, PAVE anticipates meeting the following overall milestones of: 1) understanding early life immunity and early antiretroviral treatment on the composition and stability of the latent reservoir, including in naïve T cells, and potential for HIV-1 remission; 2) eliminating of these reservoirs in pre-clinical studies of immune-targeted strategies; 3) defining the role of myeloid cells in HIV-1 persistence and rebound, including in the CNS; 4) establishing novel approaches to enhance pediatric immunity through active and passive immunization; 5) developing cutting-edge approaches to quantify and monitor proviral reservoirs to measure clinical trial efficacy, and 6) promoting active community engagement in pediatric HIV-1 cure research. These milestones will help achieve the vision of sustained ART-free control of HIV-1 replication in pediatric populations.

抽象的在静止记忆CD4+ T细胞中立即建立潜在的HIV-1储存器，无法治愈HIV-1治疗，儿童一生中令人信服的艺术。 PAVE合作的使命是使用尖端科学为了建立对小儿HIV-1储层的免疫发病的深刻而广泛的理解，年龄频谱，并证明了新型治疗对放射性储量的临床前安全性和效率并控制反弹，这将为将来的介入人类研究铺平道路 HIV-1控制艺术。我们假设婴儿免疫系统的独特特征储层建立会影响长期病毒持续性的特征，对免疫的敏感性与成人感染不同的介导的清除和重新激活，警告深入调查告知适合儿童的治疗疗法。我们将检验这一假设并执行铺路科学通过完成以下特定目的议程：1。定义的建立和演变围产期感染中的艾滋病毒潜伏储库。 2。增强小儿免疫并广泛中和抗体（BNAB）递送以实现对ART的HIV-1的治疗后控制。 3。部署免疫目标消除病毒水库的策略。 4。优化病毒学，免疫学和成像方法评估HIV-1/S（H）IV治疗效率。 5。寄养社区参与儿科艾滋病毒治愈研究。 PAVE计划是多学科，多学科和迭代的，具有敏捷的结构由四个高度协同的研究重点和一个国内和国际社会计划所包含这将迅速结合我们利益相关者的新科学方向和反馈。铺路领导团队跨越潜水的科学专业知识，并在性别，学术级和原产地。每个研究焦点还包括初级教师共同研究员，以促进他们的职业生涯 HIV-1研究领域的发展。通过我们科学领导的集体努力，执行委员会，科学顾问委员会，研究人员，行业合作伙伴，网络合作以及国内和国际社会计划，PAVE预计将达到以下整体里程碑： 1）了解早期生命免疫力和早期抗逆转录病毒治疗的成分和稳定性潜在储层，包括幼稚的T细胞，以及HIV-1缓解的潜力； 2）消除这些水库针对免疫靶向策略的临床前研究； 3）定义髓样细胞在HIV-1持久性和反弹，包括中枢神经系统； 4）建立新的方法以通过主动来增强小儿免疫和被动免疫抑制； 5）开发最先进的方法来量化和监视提供商的水库测量临床试验效率，6）促进社区参与儿科HIV-1治疗研究。这些里程碑将有助于实现小儿对HIV-1复制的持续无艺术控制的愿景人群。