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

这将是第一次使用Prime-Boost HiVis DNA和MVA-Cmdr治疗性疫苗的儿科研究。我们的 目标是开发治疗性艾滋病毒疫苗，以减少艾滋病毒携带者儿童和青年中的艾滋病毒蓄积物。我们的 科学前提是，主要增强的HiVis DNA和MVA-Cmdr疫苗可诱导细胞和体液 免疫反应对清除受感染细胞很重要。他们被选为儿童的基础上充分 成人安全数据。早期治疗的儿童是研究治疗性艾滋病毒疫苗的理想人群 因为它们健康的免疫力和较小的艾滋病毒宿主。我们将探索一种新的战略，给出一个 含有Toll样受体(TLR)4激动剂佐剂的人乳头瘤病毒特许疫苗 增强对HiVis DNA的免疫反应。参与者将是来自南非的儿童。这个项目是 在EPIICAL联盟下概念化，并将与美国军方合作进行 艾滋病毒研究计划。EPIICAL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，将推动治疗性研究的发展 面向儿童的疫苗战略。 在这项为期72周的研究中，最多将有25名参与者。参与者的年龄在9岁到25岁之间 老年人在6个月前开始服用艾滋病毒药物，并受到病毒抑制。他们将是随机的 分配给HIV疫苗组(n=10)、HIV疫苗+TLR4激动剂组(n=10)和对照组(无干预)(n=5)。 HIV DNA疫苗将在O周和4周接种，TLR4激动剂将在0周、4周和24周接种，24周将接种 MVA-Cmdr为36例。我们将广泛测量艾滋病毒宿主和免疫反应的变化 干预后。 目的1：定量和表征HiVis DNA±TLR4激动剂和 MVA-Cmdr疫苗接种 目的2：研究疫苗接种前后HIV特异性细胞和体液免疫反应的特征 并评估它们与艾滋病毒储存库终点的关系。 所产生的知识将有助于优化治疗性艾滋病毒疫苗策略，并发挥 对儿童和青年艾滋病毒治疗研究的持续影响。

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.