Role of Dendritic Cells in HIV-Immunotherapy

Abstract

HIV remains one of the most important deadly infections today, due to the lack of a preventive vaccine and limited access to medical care in developing countries. In developed countries, antiretroviral therapy is available, but it can not eliminate the virus, implying that life-long therapy is necessary. Therefore, it is important that other strategies such as therapeutic vaccination will be developed to control virus replication or even eliminate the virus. The major obstacles towards such a strategy are the huge variability of the virus and the profound HIV-induced immune dysfunction. In this review we focus on dendritic cell based immunotherapies against HIV. To develop an efficient immunotherapy, several elements should be taken into account such as which antigen and loading strategy to use, how to deliver the immunogen, how to optimize the interaction between antigenic peptide and T cells and avoid tolerance. Clearly, to develop an immunotherapy to complement the effect of HAART, it is not sufficient to enhance T cell responses against a consensus sequence or against the prevailing plasma virus. Broad and potent immune response are needed to suppress the entire quasispecies, including the latent reservoir, and to prevent any escape.

Efficient generation of antigen-specific CTLs by the BAFF-activated human B Lymphocytes as APCs: a novel approach for immunotherapy

“…However, the generation of a population of HIV-1 antigen-loaded APCs is still required to elicit strong CTL responses for anti-HIV-1 immunotherapy [55]. To generate a sufficient amount of high-quality CTLs from HIV-1-infected individuals, we tried to use the HIV-1 peptide-pulsed CD40L-sBAFF-B cells as APCs.…”

“…Although activated B cells have been identified as alternative APCs for cancer immunotherapy in a series of in vitro experiments, their functionalities in cancer immunotherapy still need to be further analyzed due to the lack of evidence from in vivo experiments [8, 55]. To verify that CD40L-sBAFF-B cells were efficient in vivo , we took advantage of an extensively studied melanoma xenograft model system.…”

“Wrapped Up” Vaccines in the Context of HIV-1 Immunotherapy

“…They include the use of inactivated virus [104,160], recombinant viral proteins [107,[161][162][163], peptides [101,164], DNA [165][166][167] and mRNA [168][169][170][171][172]. After loading, DCs are matured using various maturation cocktails composed of cytokines (such as type 1 (α,β) or type 2 (γ) interferons, TNF-α, IL-6) prostaglandines (PG), TLR ligands, T cell derived products (CD40L) or small interfering RNA (siRNA) against suppressors of cytokine signaling (SOCS)-1 [98,151].…”

Myeloid dendritic cells in HIV-1 infection

“…As potent antigen presenting cells, mDCs can be loaded with antigen ex vivo and administered as preventative or therapeutic vaccines [63]. A recent study showed that the T cell responses induced by gag mRNA loaded moDCs were polyfunctional and exhibited a memory phenotype [64].…”