Dendritic cell-based therapeutic vaccine elicits polyfunctional HIV-specific T-cell immunity associated with control of viral load

Abstract

Efforts aimed at restoring robust immune responses limiting human immunodeficiency virus (HIV)-1 replication therapeutically are warranted. We report that vaccination with dendritic cells generated ex vivo and loaded with HIV lipopeptides in patients (n = 19) on antiretroviral therapy was well tolerated and immunogenic. Vaccination increased: (i) the breadth of the immune response from 1 (1-3) to 4 (2-5) peptide-pool responses/patient (p = 0.009); (ii) the frequency of functional T cells (producing at least two cytokines among IFN-γ, TNF-α, and IL-2) from 0.026 to 0.32% (p = 0.002) and from 0.26 to 0.35% (p = 0.005) for CD4(+) and CD8(+) T cells, respectively; and (iii) the breadth of cytokines secreted by PBMCs upon antigen exposure, including IL-2, IFN-γ, IL-21, IL-17, and IL-13. Fifty percent of patients experienced a maximum of viral load (VL) 1 log10 lower than the other half following antiretroviral treatment interruption. An inverse correlation was found between the maximum of VL and the frequency of polyfunctional CD4(+) T cells (p = 0.007), production of IL-2 (p = 0.006), IFN-γ (p = 0.01), IL-21 (p = 0.006), and IL-13 (p = 0.001). These results suggest an association between vaccine responses and a better control of viral replication. These findings will help in the development of strategies for a functional cure for HIV infection.

Keywords: Antiretroviral therapy interruption; Dendritic cell; Lipopeptides; T cells; Vaccination.