Targeting HIV reservoirs in children with HIVIS DNA and MVA-CMDR vaccines

使用 HIVIS DNA 和 MVA-CMDR 疫苗针对儿童中的 HIV 储存者

• 批准号: 10700241
• 负责人: Paolo Palma
• 金额: $ 151.9万
• 依托单位: HENRY M. JACKSON FDN FOR THE ADV MIL/MED
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10700241
• 关键词: Adherence; Adjuvant; Adult; Age Months; Agonist; Antibodies; Antigens; Binding; Biological Assay; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; CD8B1 gene; Cells; Cervarix; Child; Childhood; Clinical Trials; Collaborations; DNA; Data; Dendritic Cells; Enrollment; Failure; Frequencies; Funding; Generations; Goals; Grant; HIV; HIV vaccine; Human Papillomavirus; Immune; Immune response; Immunity; Immunologic Surveillance; Infant; Intervention; Knowledge; Licensing; Measures; Military Personnel; Mississippi; Modality; Oral; Participant; Pharmaceutical Preparations; Phase; Plasma; Population; RNA; RNA Splicing; Randomized; Recommendation; Regimen; Research; Safety; Sampling; South Africa; T cell response; TLR4 gene; Therapeutic; Vaccination; Vaccines; Viral; Viremia; Virus; Youth; adaptive immune response; antibody-dependent cell cytotoxicity; antiretroviral therapy; cohort; immunogenicity; neutralizing antibody; novel strategies; open label; perinatal HIV; post intervention; programs; randomized, clinical trials; sharing platform; therapeutic development; therapeutic vaccine; vaccine strategy

This will be the first pediatric study with prime-boost HIVIS DNA and MVA-CMDR therapeutic vaccines. Our goal is to develop therapeutic HIV vaccines to reduce the HIV reservoirs in children and youth with HIV. Our scientific premise is that the prime-boost HIVIS DNA and MVA-CMDR vaccines induce cellular and humeral immune responses important for clearing infected cells. They were selected for children based on ample adult safety data. Early treated children are an ideal population to investigate therapeutic HIV vaccines because of their healthy immunity and small HIV reservoirs. We will explore a novel strategy of giving a licensed vaccine against human papilloma virus that contains toll-like receptor (TLR) 4 agonist adjuvant to boost immune responses to HIVIS DNA. Participants will be children from South Africa. The project was conceptualized under the EPIICAL Consortium and will be conducted in collaboration with the U.S Military HIV Research Program. EPIICAL does not provide any funding for this study but provides a platform for sharing expertise, data and samples from cohorts that will propel the development of therapeutic vaccine strategies for children forward. A maximum of twenty-five participants will be enrolled in this 72-week study. Participants will be 9 to 25 years old, have started HIV medications prior to 6 months of age and are virally suppressed. They will be randomly assigned to HIV vaccines (n=10) vs. HIV vaccines+ TLR4 agonist (n=10) vs. control (no interventions) (n=5). Vaccines will be given at weeks O and 4 for HIVIS DNA, weeks 0, 4 and 24 for TLR4 agonist, and weeks 24 and 36 for MVA-CMDR. We will extensively measure the changes of HIV reservoirs and immune responses post interventions. Aim 1: To quantitate and characterize the HIV reservoirs before and after HIVIS DNA ± TLR4 agonist and MVA-CMDR vaccination Aim 2: To characterize HIV-specific cellular and humeral immune responses before and after vaccination and assess their relationship to the HIV reservoir endpoints. The knowledge generated will contribute to the optimization of therapeutic HIV vaccine strategies and exert sustained influence on HIV cure research for children and youth.

这将是第一个使用初免-加强HIV DNA和MVA-CMDR治疗性疫苗的儿科研究。我们 其目标是开发治疗性艾滋病毒疫苗，以减少感染艾滋病毒的儿童和青年的艾滋病毒储存库。我们 科学的前提是，初免-加强HIV DNA和MVA-CMDR疫苗诱导细胞和体液免疫， 免疫反应对清除感染细胞很重要。他们是根据充足的儿童选择的 成人安全数据早期治疗的儿童是研究治疗性HIV疫苗的理想人群 因为他们有健康的免疫力和较小的艾滋病病毒库。我们将探索一种新的策略， 一种针对人乳头状瘤病毒的许可疫苗，其含有Toll样受体（TLR）4激动剂佐剂， 增强对HIV DNA的免疫反应。参加者将是来自南非的儿童。该项目 在EPICAL联盟的指导下进行概念化，并将与美国军方合作进行 艾滋病毒研究计划。EPICAL不为这项研究提供任何资金，但提供了一个平台， 分享来自队列的专业知识、数据和样本，这将推动治疗药物的发展。 为儿童提供疫苗。 这项为期72周的研究将入组最多25名受试者。参与者将是9至25岁 年龄较大，在6个月大之前开始使用艾滋病毒药物，并且病毒受到抑制。他们将随机 分配至HIV疫苗（n=10）对比HIV疫苗+TLR 4激动剂（n=10）对比对照（无干预）（n=5）。 将在第0周和第4周给予HIV DNA疫苗，在第0周、第4周和第24周给予TLR 4激动剂疫苗，以及在第24周给予TLR 4激动剂疫苗。 MVA-CMDR为36例。我们将广泛测量HIV宿主和免疫应答的变化 干预后。 目的1：定量和表征HIVIS DNA ± TLR 4激动剂和 MVA-CMDR疫苗接种 目的2：描述疫苗接种前后HIV特异性细胞和体液免疫应答的特征 并评估它们与HIV储库终点的关系。 所产生的知识将有助于优化治疗性艾滋病毒疫苗策略， 对儿童和青年艾滋病毒治疗研究的持续影响。