Dendritic Cell-Based Immunotherapies to Fight HIV: How Far from a Success Story? A Systematic Review and Meta-Analysis

Abstract

The scientific community still faces the challenge of developing strategies to cure HIV-1. One of these pursued strategies is the development of immunotherapeutic vaccines based on dendritic cells (DCs), pulsed with the virus, that aim to boost HIV-1 specific immune response. We aimed to review DCs-based therapeutic vaccines reports and critically assess evidence to gain insights for the improvement of these strategies. We performed a systematic review, followed by meta-analysis and meta-regression, of clinical trial reports. Twelve studies were selected for meta-analysis. The experimental vaccines had low efficiency, with an overall success rate around 38% (95% confidence interval = 26.7%–51.3%). Protocols differed according to antigen choice, DC culture method, and doses, although multivariate analysis did not show an influence of any of them on overall success rate. The DC-based vaccines elicited at least some immunogenicity, that was sometimes associated with plasmatic viral load transient control. The protocols included both naïve and antiretroviral therapy (ART)-experienced individuals, and used different criteria for assessing vaccine efficacy. Although the vaccines did not work as expected, they are proof of concept that immune responses can be boosted against HIV-1. Protocol standardization and use of auxiliary approaches, such as latent HIV-1 reservoir activation and patient genomics are paramount for fine-tuning future HIV-1 cure strategies.

Lentiviral Vector-Based Dendritic Cell Vaccine Suppresses HIV Replication in Humanized Mice

“…24 Dendritic cell (DC) vaccines that exploit the ability of the cells to initiate T cell responses have been explored as a means to enhance T cell responses to cancer and other chronic diseases, including HIV-1. [25][26][27][28] In DC vaccine strategies, patient monocytes are isolated from peripheral blood mononuclear cells (PBMCs) and differentiated in culture to monocyte-derived DCs (MDDCs) and then pulsed with synthetic peptide epitopes, tumor whole-cell extract, or viral lysate, or alternatively, electroporated with antigen-encoding synthetic mRNA. The treated cells are activated with a cocktail of cytokines and then reinfused.…”

Role of Dendritic Cells in Exposing Latent HIV-1 for the Kill

“…Overall, although DC-based HIV-1 immunotherapies have proven to be safe and well tolerated, they have achieved a success rate of only 38% according to meta-analyses [210]. Furthermore, while there have been many DC-based therapeutic approaches explored in HIV clinical trials, there has been little consensus with regards to the selection of subjects, methods of DC generation and preparation, choice of immunogen, and assessment of immunologic and virologic responses [211].…”

An immunoregulatory role of dendritic cell-derived exosomes versus HIV-1 infection: take it easy but be warned

“…Other researchers loaded DCs with a whole inactivated virus (32,33,38) The protocols used for the maturation of antigenloaded DCs were also different. Generally, in most studies, investigators supplemented the culture medium with cytokines as follows: GM-CSF, IFN-α, interleukin-1β (IL-1β), IL-4, IL-6, and tumor necrosis factor (TNF)-α (27). In all studies, vaccines were injected percutaneously in different doses varying from 2×10 6 (33,36) to 1.2×10 7 (40) cell per dose.…”

“…Loading of autologous virus-free DCs with a HIV-1-specific antigen with subsequent vaccination of a HIV-1 infected individual with antigen-activated DCs was suggested to boost the restoration of the host anti-viral immune response (26). Basically, any viral product such as a whole autologous heator chemically-inactivated virus particles, viral peptides (such as pol and gag) or viral RNA transcripts may serve as an antigen for generation of DC-based vaccines (27).…”