Background
Therapeutic vaccines offer a promising approach to decrease HIV reservoirs, enhance immunity and enable ART-free remission. This study characterizes HIV-specific T and humoral responses following prime-boost vaccination of the HVRRICANE trial: HIVIS DNA and MVA-CMDR vaccines ± the TLR4 agonist with Cervarix HPV vaccine co-administration.
Methods
HVRRICANE enrolled 25 South African adolescents with perinatal HIV, virally suppressed (VL<200 copies/ml) on ART since 6 mo of age. The trial design is in Fig 1. Comprehensive evaluations included viral reservoirs and immunogenicity assements. HIV-specific T cells were longitudinally tested by IFN-γ/IL-2 Fluorospot assays, stimulating thawed PBMCs with GAG or ENV peptide pools. Activation Induced Molecules (AIM)/Intracellular Cytokine Staining (ICS) assays complemented these analyses, along with Western Blot (WB) serology for Abs against 10 HIV-1 antigens.
Results
Overall, we observed a sustained rise in HIV-specific T cell responses following vaccination, which remained high over time. At wk60, IFN-γ, IL-2 and combined IFN-γ/IL-2 responses to GAG and ENV stimulation increased from baseline (wk0). Comparisons among all time points within arms showed that in Arm 2, IL-2, IFN-γ and poly-functional T cells increased during the vaccination in response to GAG (p=0.0486, p=0.0057, p=0.0477). Arm 2 also exhibited higher IFN-γ production response to ENV (p=0.0012). Comparisons at each time point between arms revealed significant differences in IFN-γ response to GAG and ENV at wk0 across all arms (p=0.0133, p=0.0297) and between Arms 2 and 3 (3 > 2, p=0.0321, p=0.0085). Differences in IL-2-producing T cells to ENV were noted between Arm 2 and 3 (3 > 2, p=0.0433). IFN-γ-producing T cells showed significant differences between Arms 1 and 2 (1 > 2, p=0.0091) after GAG stimulation. At wk40 (after normalizing for wk0) IFN-γ responses differed between Arms 1 and 2 (2 > 1) to both GAG (p=0.0452) and ENV (p=0.0312), with further differences at wk48 between Arms 2 and 3 to ENV (2 > 3, p=0.0321). Significant differences in WB score were noted among groups at wk0 (p=0.0352). Increases in both p24 (p=0.0156) and WB (p=0.0391) scores over time were found in Arm 1. No variation in single copy viral load was detected among and within Arms.
Conclusions
Data show strong and lasting HIV-specific immunity from the vaccine regimens tested, paving the way for immunotherapy to reduce the viral reservoir in children and youths with HIV.