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.
Highlights
The adaptive immune response during viral infections is mediated by antigen-presenting cells (APC), such as macrophages, B lymphocytes and dendritic cells (DCs), which capture antigens and present them to naïve lymphocytes [1,2].Immature DCs are characterized by high endocytic capacity, with constant sampling of the surroundings of peripheral tissues for pathogen and injury sensing.Int
The authors usually assessed the immune response in each experimental vaccine study by comparing pre-vaccination and post-vaccination peripheral blood mononuclear cells (PBMC) samples to assess cytokine expression and cytotoxic T lymphocytes (CTL) activity by standard techniques such as enzyme-linked immunosorbent assay (ELISA) [7,16], intracellular cytokine staining followed by flow cytometry analysis [6,8,13,14,16], Luminex® multiplex bead-based cytokine assay [14] or IFN-γ enzyme-linked immunospot (ELISPOT) assays [5,10,11,12,14,15]
Some studies showed that monocyte-derived DC from antiretroviral therapy (ART) patients produced lower levels of IL-12 after CD40L induction [17], while IL-12 reduced levels are associated with no viral load control after DC-vaccination [6]
Summary
The adaptive immune response during viral infections is mediated by antigen-presenting cells (APC), such as macrophages, B lymphocytes and dendritic cells (DCs), which capture antigens and present them to naïve lymphocytes [1,2].Immature DCs are characterized by high endocytic capacity, with constant sampling of the surroundings of peripheral tissues (such as mucosa and epithelia) for pathogen and injury sensing.Int. The adaptive immune response during viral infections is mediated by antigen-presenting cells (APC), such as macrophages, B lymphocytes and dendritic cells (DCs), which capture antigens and present them to naïve lymphocytes [1,2]. Immature DCs are characterized by high endocytic capacity, with constant sampling of the surroundings of peripheral tissues (such as mucosa and epithelia) for pathogen and injury sensing.
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