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

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.