Dendritic cell based vaccines for HIV infection: the way ahead

Abstract

Dendritic cells have a central role in HIV infection. On one hand, they are essential to induce strong HIV-specific CD4⁺ helper T-cell responses that are crucial to achieve a sustained and effective HIV-specific CD8⁺ cytotoxic T-lymphocyte able to control HIV replication. On the other hand, DCs contribute to virus dissemination and HIV itself could avoid a correct antigen presentation. As the efficacy of immune therapy and therapeutic vaccines against HIV infection has been modest in the best of cases, it has been hypothesized that ex vivo generated DC therapeutic vaccines aimed to induce effective specific HIV immune responses might overcome some of these problems. In fact, DC-based vaccine clinical trials have yielded the best results in this field. However, despite these encouraging results, functional cure has not been reached with this strategy in any patient. In this Commentary, we discuss new approaches to improve the efficacy and feasibility of this type of therapeutic vaccine.

Keywords: HIV; T cell responses; dendritic cells; functional cure; therapeutic vaccine.

Figure 1. Levels of a-defensins 1–3 produced by imMDDC from HIV-infected individuals. (A) Comparison between the secreted levels of α-defensins 1–3 by imMDDC from HIV-controllers (elite controllers and viremic controllers; n = 13) and HIV non-controllers (viremic non-controllers and patients with HAART; n = 16). Bars indicated the mean of α-defensins 1–3 and error bars represent the SEM from the mean of the replicates.

Figure 2. Highest and lowest decrease in pVL set-point in vaccinees and controls (as defined as the highest and lowest difference between pVL set-point at any time point after cART interruption and baseline pVL set-point before any cART). There were significantly different between arms [highest decrease (or peak decrease): mean ∆log₁₀ -1.2 vs -0.56 copies/ml, in vaccinees vs controls, p = 0.014; lowest decrease: mean ∆log₁₀ -0.54 vs -0.06 copies/ml, in vaccinees vs controls, p = 0.04].

Figure 3. ADA increases proliferation and IFN-γ secretion in co-cultures of HIV-inactivated-pulsed DC and autologous T cells of HIV-1-infected individuals. (A) T-cell proliferation in a 7 d assay, measured as c.p.m. of [³H]-thymidine incorporation during last 18 h of co-culture in absence (white columns) or presence (black columns) of ADA (B) IFN-γ secretion in absence (white), or presence (black) of ADA at day 2 of co-culture of T cells with DC pulsed with inactivated HIV-1 BaL (30 min heat inactivated). Bars indicated the mean of proliferation and IFN-γ secretion, respectively, and error bars represent the SEM from the mean of the replicates (n = 8).