Background
Vaccine mediated induction of novel broad HIV-specific CD8+ cytotoxic T cells and binding antibodies (Ab) with effector function is a strategy for clearance of the HIV reservoir. Youth acquiring HIV in the perinatal period and initiated antiretroviral therapy (ART) in the first 6 months of life tend to have robust immune responses and small HIV reservoirs. The RV534 Phase 1 study was an open-label randomized proof-of-concept study to evaluate the safety and effects of prime-boost HIVIS DNA and MVA-CMDR vaccine regimens with or without Cervarix, containing AS04 adjuvant, a Toll-like receptor 4 agonist, on HIV reservoirs and their relationship to HIV-specific humoral and cellular immune responses in perinatally infected youth.
Methods
Perinatally HIV infected youth (n=25) median age 15 years, initiating ART in the first 6 months of life with consistent viral suppression, entry viral load <200 cps/ml and CD4 T cell count >400 cells/mm3 were enrolled at study site in Cape Town, South Africa. Participants were randomized and administered the vaccine HIVIS DNA (1500 µg, wks 0, 4) and MVA-CMDR (1×108 IU, wks 24, 36), Arm 1 (n=10); the vaccines along with Cervarix, Arm 2 (n=10); and Cervarix alone (wks 0, 4, 24), Arm 3 (n=5). Antigen-specific IgG binding Ab against Env and Gag were measured at wks -2 (baseline), 8, 28, 40 and 60 by ELISA and/or multiplex Luminex®-based assay.
Results
The vaccine regimen was well tolerated with no vaccine related serious adverse events. Cervarix alone (Arm 3) did not induce HIV Env or Gag Ab responses. Binding IgG Abs against Env and Gag were present at baseline. HIVIS DNA alone did not induce HIV Env or Gag Ab responses. However, MVA-CMDR induced higher HIV Env Ab responses in Arms 1 and 2. HIV Env Ab responses were significantly higher (2-5 fold) than Cervarix alone (Arm 3) (p<0.05) across a multi-subtype antigen panel. Peak Env-specific Ab responses were observed at wk 40. MVA-CMDR boosts also significantly increased the Gag-specific Ab responses to subtype A and B by 3-5 fold (p<0.05) from baseline. Peak Gag-specific Ab responses were observed at wk 28 and subtype B Gag specific Abs were sustained through wk 60. The addition of Cervarix (Arm 2 vs Arm 1) did not increase Ab responses.
Conclusions
The HIVIS DNA and MVA-CMDR combination potently induced antibody responses, against both HIV Env and Gag in perinatally infected youth. Correlation of vaccine induced Ab responses and their effect on the HIV reservoir are currently underway.