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

总结 这将是第一个在儿科进行的联合治疗性HIV疫苗研究。我们的目标是开发治疗 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库。我们的科学前提是 初免-加强免疫HIVIS DNA和MVA-CMDR疫苗诱导重要的细胞和体液免疫应答 用于清除受感染的细胞。根据充足的成人安全性数据，选择儿童使用。包括早期 由于儿童的免疫力健康，艾滋病毒储存量小，因此接受了治疗。其他新组件包括 提供一种含有Toll样受体（TLR）4激动剂的已获许可的抗人乳头瘤病毒疫苗 佐剂，以增强对HIV DNA的免疫反应。我们还将为仅有的10名艾滋病毒感染者提供MVA-CMDR 全世界以前有艾滋病毒DNA的儿童，因为这种晚期加强策略在成人中显示出增强 疫苗免疫。我们将包括来自南非、泰国和意大利的儿童， 这一优势将支持结果对全球流行病的普遍性。项目 将在EPICAL联盟和美国的保护伞下进行。军事艾滋病毒研究计划 致力于开发治疗性艾滋病疫苗，作为缓解艾滋病的策略。 35名参与者将参加这项为期48周的研究，其中包括25名9至18岁的艾滋病毒感染者 在6个月大之前服用药物，并抑制病毒。他们将被随机分配到艾滋病毒 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）。疫苗将 在第0、4和12周给予HIVIS DNA和TLR 4激动剂，在第24和36周给予MVA-CMDR。 MVA-CMDR晚期增强7年后，HIV DNA将在10名14至24岁的意大利青年中进行评估。 我们将广泛测量艾滋病毒宿主的变化和干预后的免疫反应。 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， 评估它们与HIV储库终点的关系。 目的3：定量和表征先前在青年中的免疫原性和HIV储库终点 接种HIVIS DNA并接受MVA-CMDR晚期加强。 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。

Summary This will be the first combined therapeutic HIV vaccine study in pediatrics. 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 humoral immune responses important for clearing infected cells. They were selected for children based on ample adult safety data. We include early treated children because of their healthy immunity and small HIV reservoirs. Other novel components include giving a licensed vaccine against human papilloma virus that contains toll-like receptor (TLR) 4 agonist adjuvant to boost immune responses to HIVIS DNA. We will also give MVA-CMDR to the only 10 HIV-infected children worldwide that previously had HIVIS DNA as this late boost strategy was shown in adults to enhance immunity to vaccines. We will include children from South Africa, Thailand and Italy infected with different clades of HIV - a strength that will support the generalizability of the results to the global epidemic. The project will be conducted under the umbrella of the EPIICAL Consortium and the US. Military HIV Research Program that is dedicated to developing therapeutic HIV vaccines as a strategy towards an HIV remission. Thirty-five participants will be in this 48-week study including 25 that are 9 to 18 years old who 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 0, 4 and 12 for HIVIS DNA and TLR4 agonist, and weeks 24 and 36 for MVA-CMDR. The MVA-CMDR late boost 7 years after HIVIS DNA will be evaluated in 10 Italian youth aged 14 to 24 years old. 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 humoral immune responses before and after vaccination and assess their relationship to the HIV reservoir endpoints. Aim 3: To quantitate and characterize the immunogenicity and HIV reservoir endpoints in youth previously vaccinated with HIVIS DNA and receiving MVA-CMDR late boost. 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.