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

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Principal Investigator: Paolo  Palma
Organization: HENRY M. JACKSON FDN FOR THE ADV MIL/MED
Fiscal Year: 2024
Award: $983,724
Funding agency: National Institute of Allergy and Infectious Diseases

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.

Terms: <0-11 years old><21+ years old><AIDS Virus><Ab-dependent cellular cytotoxicity><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Adherence><Adjuvant><Adult><Adult Human><Age Months><Agonist><Antibodies><Antigens><Armed Forces Personnel><Assay><Binding><Bioassay><Biological Assay><Blood Plasma><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><CD8><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><CD8B><CD8B1><CD8B1 gene><Cell Body><Cells><Cervarix><Child><Child Youth><Childhood><Children (0-21)><Clinical Trials><Collaborations><DNA><Data><Dendritic Cells><Deoxyribonucleic Acid><Drugs><Enrollment><Failure><Frequencies><Funding><Generations><Goals><Grant><HIV><HIV vaccine><HIV/AIDS Vaccines><HPV><Homolog of Drosophila TOLL><Human Immunodeficiency Viruses><Human Papilloma Virus><Human Papillomavirus><Immune><Immune Surveillance><Immune response><Immunes><Immunity><Immunologic Surveillance><Immunologic Surveillances><Immunological Surveillance><Immunological Surveillances><Immunological response><Immunosurveillance><Infant><Infectious Human Wart Virus><Intervention><Intervention Strategies><Knowledge><LAV-HTLV-III><LYT3><Licensing><Lymphadenopathy-Associated Virus><Measures><Medication><Military><Military Personnel><Mississippi><Modality><Molecular Interaction><Non-Polyadenylated RNA><Oral><Participant><Pharmaceutical Preparations><Phase><Plasma><Plasma Serum><Population><RNA><RNA Gene Products><RNA Splicing><Randomized><Recommendation><Regimen><Research><Reticuloendothelial System, Serum, Plasma><Ribonucleic Acid><Safety><Sampling><South Africa><Splicing><T cell response><T4 Cells><T4 Lymphocytes><T8 Cells><T8 Lymphocytes><TLR4><TLR4 gene><Therapeutic><Toll Homologue><Vaccination><Vaccines><Veiled Cells><Viral><Viremia><Virus><Virus-HIV><Youth><Youth 10-21><adaptive immune response><adulthood><antibody dependent cell mediated cytotoxicity><antibody dependent cytotoxicity><antibody mediated cellular cytotoxicity><antibody-dependent cell cytotoxicity><antibody-dependent cellular cytotoxicity><antibody-mediated cytotoxicity><antiretroviral therapy><antiretroviral treatment><cohort><drug/agent><enroll><host response><human immunodeficiency virus vaccine><immune response to vaccination><immune response to vaccines><immune system response><immunogen><immunogenicity><immunoresponse><interventional strategy><kids><military population><neutralizing antibody><new approaches><novel approaches><novel strategies><novel strategy><open label><open label study><pediatric><perinatal HIV><post intervention><programs><randomisation><randomization><randomized, clinical trials><randomly assigned><shareable platform><sharing platform><therapeutic agent development><therapeutic development><therapeutic vaccine><toll-like receptor 4><treatment vaccines><vaccine associated immune response><vaccine for the treatment><vaccine for treatment><vaccine immune response><vaccine immunogenicity><vaccine induced immune response><vaccine strategy><viraemia><viral sepsis><virusemia><wart virus><youngster>