Safety and Effects of Using Prime-boost HIVIS DNA and MVA-CMDR Vaccine Regimens With or Without Toll-like Receptor 4 Agonist on HIV Reservoirs in Perinatally HIV Infected Children and Youth
- Conditions
- HIV Infections
- Interventions
- Biological: CervarixBiological: HIVIS DNA/MVA-CMDRBiological: HIVIS DNA + Cervarix and MVA-CMDR
- Registration Number
- NCT04301154
- Lead Sponsor
- Henry M. Jackson Foundation for the Advancement of Military Medicine
- Brief Summary
Phase I, Proof of Concept, Open-Label, Randomized Clinical Trial to Evaluate the Safety and Effects of Using Prime-boost HIVIS DNA and MVA-CMDR Vaccine Regimens with or without Toll-like Receptor 4 Agonist on HIV Reservoirs in Perinatally HIV Infected Children and Youth
- Detailed Description
HIVIS DNA and MVA-CMDR vaccines induce immune responses important for clearing infected cells: broad HIV-specific CD8+ cytotoxic T cells, potent antibodydependent cellular cytotoxicity (ADCC), and binding antibody (Ab) and neutralizing antibody (NAb). The study include early treated children because of their healthy immunity and small HIV reservoirs. Giving licensed vaccine, Cervarix®, against human papilloma virus (HPV) that contains toll-like receptor (TLR) 4 agonist with HIVIS DNA could increase DNA antigen loading on dendritic cells and promote adaptive immune responses to the HIV vaccine.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 25
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 3 (n=5): Cervarix Cervarix Arm 3 (n=5) will receive 0.5 ml of Cervarix by IM needle injection at weeks 0, 4 and 24. Arm 1 (n=10): HIVIS DNA / MVA-CMDR HIVIS DNA/MVA-CMDR Arm 1 (n=10) will receive 1500 micrograms (0.5ml) HIVIS DNA IM by needle-free injection at weeks 0 and 4 followed by intramuscular (IM) needle injection of 1 X 108 IU/mL (1ml) MVA-CMDR at weeks 24 and 36 in the same arm as HIVIS DNA. Participants who have been randomized to receive HIVIS DNA and MVA-CMDR alone (ARM 1) will be administered Cervarix after week 72, the last study follow-up visit, if required. Arm 2 (n=10): HIVIS DNA + Cervarix/ / MVA-CMDR HIVIS DNA + Cervarix and MVA-CMDR Arm 2 (n=10) will receive 0.5 ml of Cervarix IM by needle injection followed by 1500 micrograms (0.5ml) per injection of HIVIS DNA IM by a needle-free injection device in the skin above (proximal to) the Cervarix injection (within 1.5 cm). They will receive 1 X 108 IU/mL (1ml) MVA-CMDR IM by needle injection at weeks 24 and 36 in the same arm as HIVIS DNA. They will also receive 0.5 ml Cervarix at the time of the first MVACMDR injection in the opposite arm from the MVA injection at week 24.
- Primary Outcome Measures
Name Time Method Solicited and unsolicited serious adverse events through study completion, an average of 1 year Safety
HIV DNA (copies/106 CD4+ T cells) Change from Baseline at week 28, 48 Efficacy
Frequencies of CD4+ T cells that produce Tat/Rev transcription (tat/rev RNA+ cells/106 CD4+ T cells) Change from Baseline at week 24, 36, 48, 60, 72 Efficacy
- Secondary Outcome Measures
Name Time Method HIV-specific CD8+ and CD4+ T cells Week 28, 48 Immunogicity
Unspliced and multiply-spliced RNA+ cells/1000 ng cellular RNA Week 24, 36, 48, 60, 72 Efficacy
Plasma HIV RNA by SCA Week 24, 36, 48, 60, 72 Efficacy
Binding and neutralizing Ab Week 28, 48 Immunogicity
Solicited and unsolicited non-serious adverse events through study completion, an average of 1 year Safety
IUPM from total CD4+ T cells in blood by QVOA Week 24, 36, 48, 60, 72 Efficacy
ADCC Week 28, 48 Immunogicity
Gene expression on HIV-specific CD8+ and CD4+ T cells Week 28, 48 immune response
Global gene expression on PBMCs by RNA seq Week 28, 48 immune response
Trial Locations
- Locations (1)
Stellenbosch University
🇿🇦Tygerberg Hills, Cape Town, South Africa