Loading dendritic cells with PLA-p24 nanoparticles or MVA expressing HIV genes induces HIV-1-specific T cell responses

Climent, Núria; Munier, Sevérine; Piqué, Núria; García, Felipe; Pavot, Vincent; Primard, Charlotte; Casanova, Víctor; Gatell, José M.; Verrier, Bernard; Gallart, Teresa

doi:10.1016/j.vaccine.2014.09.010

Cited by 19 publications

(8 citation statements)

References 67 publications

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“…Previously, Au-NPs were used to IgG delivery in rabbit retina [49] and as adjuvant to improve immunization in spinal cord of injured rats [50]. PLA-NPs were used to carry Gag p24 HIV-1 antigen to increase immune response in mice [51] and T-cell responses on HIV-infected patients [52]. PEG-PLA-NPs were also used to delivery betamethasone in cochlea, promoting attenuation of cochlear hair cells loss induced by traumatic noise in mice [53].…”

Section: Introductionmentioning

confidence: 99%

Suitability of 3D human brain spheroid models to distinguish toxic effects of gold and poly-lactic acid nanoparticles to assess biocompatibility for brain drug delivery

et al. 2019

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Background The blood brain barrier (BBB) is the bottleneck of brain-targeted drug development. Due to their physico-chemical properties, nanoparticles (NP) can cross the BBB and accumulate in different areas of the central nervous system (CNS), thus are potential tools to carry drugs and treat brain disorders. In vitro systems and animal models have demonstrated that some NP types promote neurotoxic effects such as neuroinflammation and neurodegeneration in the CNS. Thus, risk assessment of the NP is required, but current 2D cell cultures fail to mimic complex in vivo cellular interactions, while animal models do not necessarily reflect human effects due to physiological and species differences. Results We evaluated the suitability of in vitro models that mimic the human CNS physiology, studying the effects of metallic gold NP (AuNP) functionalized with sodium citrate (Au-SC), or polyethylene glycol (Au-PEG), and polymeric polylactic acid NP (PLA-NP). Two different 3D neural models were used (i) human dopaminergic neurons differentiated from the LUHMES cell line (3D LUHMES) and (ii) human iPSC-derived brain spheroids (BrainSpheres). We evaluated NP uptake, mitochondrial membrane potential, viability, morphology, secretion of cytokines, chemokines and growth factors, and expression of genes related to ROS regulation after 24 and 72 h exposures. NP were efficiently taken up by spheroids, especially when PEGylated and in presence of glia. AuNP, especially PEGylated AuNP, effected mitochondria and anti-oxidative defense. PLA-NP were slightly cytotoxic to 3D LUHMES with no effects to BrainSpheres. Conclusions 3D brain models, both monocellular and multicellular are useful in studying NP neurotoxicity and can help identify how specific cell types of CNS are affected by NP. Electronic supplementary material The online version of this article (10.1186/s12989-019-0307-3) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Suitability of 3D human brain spheroid models to distinguish toxic effects of gold and poly-lactic acid nanoparticles to assess biocompatibility for brain drug delivery

et al. 2019

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“…Nevertheless, proteins are primarily processed and presented in an MHC II context and are therefore less prone to initiate a CD8 + T-cell response, which plays an important role in viral control in HIV infected individuals [5,7,52,53]. In order to increase cross-presentation to MHC I, proteins can be coupled to carriers such as amphipathic peptides, poly-lactic acid (PLA) NPs or nanostructured lipid carriers or delivered with immunomodulatory adjuvants such as CpG [54][55][56]. The easy uptake and processing of peptides by antigen presenting cells and subsequent presentation in MHC molecules, makes them interesting candidates for a booster vaccine, after mRNA…”

Section: Peptidesmentioning

confidence: 99%

Off the beaten path: Novel mRNA-nanoformulations for therapeutic vaccination against HIV

D'haese

Lacroix

García

et al. 2021

Journal of Controlled Release

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“…Treatment with heterodimeric IL-15 (hetIL-15) was used recently to decrease HIV-1 RNA in the plasma, possibly through the maintenance of natural killer (NK) cells. Specifically, hetIL-15 allows for CTL targeting of infected cells in immune privileged sites within the secondary lymphoid tissues [107]. Aside from a suboptimal efficacy, however, some effects of this treatment included the induction of anti-inflammatory processes with an increase in IL-10 production and increased expression of programmed death-1 (PD-1) [108].…”

Section: Considerations For Optimizing DC Vaccines In Future Studiesmentioning

confidence: 99%

The Evolution of Dendritic Cell Immunotherapy against HIV-1 Infection: Improvements and Outlook

Mohamed

Miller

Jennings

et al. 2020

Journal of Immunology Research

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Dendritic cells (DC) are key phagocytic cells that play crucial roles in both the innate and adaptive immune responses against the human immunodeficiency virus type 1 (HIV-1). By processing and presenting pathogen-derived antigens, dendritic cells initiate a directed response against infected cells. They activate the adaptive immune system upon recognition of pathogen-associated molecular patterns (PAMPs) on infected cells. During the course of HIV-1 infection, a successful adaptive (cytotoxic CD8+ T-cell) response is necessary for preventing the progression and spread of infection in a variety of cells. Dendritic cells have thus been recognized as a valuable tool in the development of immunotherapeutic approaches and vaccines effective against HIV-1. The advancements in dendritic cell vaccines in cancers have paved the way for applications of this form of immunotherapy to HIV-1 infection. Clinical trials with patients infected with HIV-1 who are well-suppressed by antiretroviral therapy (ART) were recently performed to assess the efficacy of DC vaccines, with the goal of mounting an HIV-1 antigen-specific T-cell response, ideally to clear infection and eliminate the need for long-term ART. This review summarizes and compares methods and efficacies of a number of DC vaccine trials utilizing autologous dendritic cells loaded with HIV-1 antigens. The potential for advancement and novel strategies of improving efficacy of this type of immunotherapy is also discussed.

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Loading dendritic cells with PLA-p24 nanoparticles or MVA expressing HIV genes induces HIV-1-specific T cell responses

Cited by 19 publications

References 67 publications

Suitability of 3D human brain spheroid models to distinguish toxic effects of gold and poly-lactic acid nanoparticles to assess biocompatibility for brain drug delivery

Suitability of 3D human brain spheroid models to distinguish toxic effects of gold and poly-lactic acid nanoparticles to assess biocompatibility for brain drug delivery

Off the beaten path: Novel mRNA-nanoformulations for therapeutic vaccination against HIV

The Evolution of Dendritic Cell Immunotherapy against HIV-1 Infection: Improvements and Outlook

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