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Pediatric Adolescent Virus Elimination (PAVE) Martin Delaney Collaboratory

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
批准号:
10620823
负责人:
Ann M Chahroudi
金额:
$590.41万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
未结题
起止时间:
2021-08-16 至 2026-04-30
关键词:
15 year oldAccelerationActive ImmunizationAddressAdherenceAdolescentAdolescent and Young AdultAdultAftercareAgeAntibody TherapyAwardBindingBiological MarkersBiological ModelsBiologyCharacteristicsChildChildhoodClinicalClinical ResearchClinical TrialsCollaborationsCommunitiesCountryDataDevelopmentDisease remissionEpidemicEpigenetic ProcessEthicsEvolutionExhibitsFacultyFeedbackFosteringFutureGenderGenerationsGoalsHIVHIV-1HumanImageImmuneImmune TargetingImmune systemImmunityImmunizationImmunologic MarkersImmunologicsImmunotherapeutic agentIndustryInfantInfectionInternationalInterruptionInterventionIntervention TrialInvestigationKnowledgeLeadershipLifeMeasuresMediatingMissionModelingMonitorMyeloid CellsOregonPassive ImmunizationPerinatal InfectionPlasmaPopulationPre-Clinical ModelPredispositionPreventionPrimatesResearchResearch PersonnelResourcesRestRoleSafetySamplingScienceShockStructureT cell responseT-LymphocyteTestingTherapeuticTimeVertical Disease TransmissionViralViral reservoirVirusVisionWorkYouthagedantiretroviral therapycareer developmentcohortcollaboratorycombatcommunity engagementcostefficacy clinical trialefficacy evaluationimaging modalityindustry partnerinfant infectioninsightlatent HIV reservoirliteracymeetingsmemory CD4 T lymphocytemultidisciplinaryneutralizing antibodynovelnovel strategiesnovel therapeuticspediatric human immunodeficiency virusperinatal HIVpre-clinicalpreclinical efficacypreclinical safetypreclinical studyprogramspurgeresponseside effectsocial stigmasynergismtechnology platformtherapy durationviral reboundyoung adult

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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.
期刊论文(5)
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会议论文
DOI: 10.1093/cid/ciac408
发表时间: 2022-08-15
期刊: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子: --
作者: []
通讯作者:
Broadly neutralizing antibodies: "The next thing" to treat children with HIV?
广泛中和抗体:治疗艾滋病毒儿童的“下一步”?
DOI: 10.1126/scitranslmed.adi0293
发表时间: 2023
期刊: Science translational medicine
影响因子: 17.1
作者: [Mavigner,Maud, Chahroudi,Ann]
通讯作者: Chahroudi,Ann
DOI: 10.1097/coh.0000000000000807
发表时间: 2023-09-01
期刊: CURRENT OPINION IN HIV AND AIDS
影响因子: 4.1
作者: [Herbert, Nicholas G., Goulder, Philip J. R.]
通讯作者: Goulder, Philip J. R.
Role of Early Life Cytotoxic T Lymphocyte and Natural Killer Cell Immunity in Paediatric HIV Cure/Remission in the Anti-Retroviral Therapy Era.
早期生命的细胞毒性T淋巴细胞和天然杀伤细胞免疫在抗逆转录病毒疗法时期的儿科HIV治疗/缓解中的作用。
DOI: 10.3389/fimmu.2022.886562
发表时间: 2022
期刊: Frontiers in immunology
影响因子: 7.3
作者: []
通讯作者:
Immune determinants of pediatric HIV/SIV reservoir establishment and maintenance
  • 批准号:
    10701467
  • 项目类别:
  • 资助金额:
    $156.37万
  • 财政年份:
    2023
  • 负责人:
    Ann M Chahroudi
  • 依托单位:
Immune determinants of pediatric HIV/SIV reservoir establishment and maintenance
  • 批准号:
    10701468
  • 项目类别:
  • 资助金额:
    $3.41万
  • 财政年份:
    2023
  • 负责人:
    Ann M Chahroudi
  • 依托单位:
Emory Pediatrics and Pathology Stimulating Access to Research in Residency (Emory-PP StARR).
  • 批准号:
    10592914
  • 项目类别:
  • 资助金额:
    $8.21万
  • 财政年份:
    2023
  • 负责人:
    Ann M Chahroudi
  • 依托单位:
Immune determinants of pediatric HIV/SIV reservoir establishment and maintenance
  • 批准号:
    10701470
  • 项目类别:
  • 资助金额:
    $54.44万
  • 财政年份:
    2023
  • 负责人:
    Ann M Chahroudi
  • 依托单位:
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