Nanoparticle Adjuvant Sensing by TLR7 Enhances CD8+ T Cell–Mediated Protection from <i>Listeria Monocytogenes</i> Infection

Lebel, Marie-Ève; Daudelin, Jean-François; Chartrand, Karine; Tarrab, Esther; Kalinke, Ulrich; Savard, Pierre; Labrecque, Nathalie; Leclerc, Denis; Lamarre, Alain

doi:10.4049/jimmunol.1302030

Cited by 56 publications

(76 citation statements)

References 65 publications

(65 reference statements)

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“…There are no previously recognised immunostimulatory reagents in eCPMV. Other self-assembling plant virus-like particles such as Papaya Mosaic Virus nanoparticles have been shown to possess adjuvant-like properties, but these were attributable to ssRNA in the particle, as immunogenicity required TLR7 26 . eCPMV is RNA-free, as determined by extensive characterisation (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

In situ vaccination with cowpea mosaic virus nanoparticles suppresses metastatic cancer

et al. 2015

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Nanotechnology has tremendous potential to contribute to cancer immunotherapy. The “in situ vaccination” immunotherapy strategy directly manipulates identified tumours to overcome local tumour-mediated immunosuppression and subsequently stimulates systemic anti-tumour immunity to treat metastases. We show that inhalation of self-assembling virus-like nanoparticles from Cowpea Mosaic Virus (CPMV) reduces established B16F10 lung melanoma and simultaneously generates potent systemic anti-tumour immunity against poorly immunogenic B16F10 in the skin. Full efficacy required Il-12, Ifn-γ, adaptive immunity, and neutrophils. Inhaled CPMV nanoparticles were rapidly taken up by and activated neutrophils in the tumour microenvironment as an important part of the anti-tumour immune response. CPMV also exhibited clear treatment efficacy and systemic anti-tumour immunity in ovarian, colon, and breast tumour models in multiple anatomic locations. CPMV nanoparticles are stable, nontoxic, modifiable with drugs and antigens, and their nanomanufacture is highly scalable. These properties, combined with their inherent immunogenicity and demonstrated efficacy against a poorly immunogenic tumour, make CPMV an attractive and novel immunotherapy against metastatic cancer.

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Section: Discussionmentioning

confidence: 99%

In situ vaccination with cowpea mosaic virus nanoparticles suppresses metastatic cancer

et al. 2015

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“…Instillation with PapMV nanoparticles triggered pro-inflammatory cytokines and chemokines secretion and immune cells recruitment shortly after treatment [10]. PapMV nanoparticles were also showed to be a TLR7 ligand, a receptor that activates innate immunity [11]. Furthermore, PapMV nanoparticles administered by the subcutaneous route were previously shown to improve and broaden the immune response to TIV in mouse and ferret animal models [7].…”

Section: Introductionmentioning

confidence: 99%

PapMV nanoparticles improve mucosal immune responses to the trivalent inactivated flu vaccine

et al. 2014

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BackgroundTrivalent inactivated flu vaccines (TIV) are currently the best means to prevent influenza infections. However, the protection provided by TIV is partial (about 50%) and it is needed to improve the efficacy of protection. Since the respiratory tract is the main site of influenza replications, a vaccine that triggers mucosal immunity in this region can potentially improve protection against this disease. Recently, PapMV nanoparticles used as an adjuvant in a formulation with TIV administered by the subcutaneous route have shown improving the immune response directed to the TIV and protection against an influenza challenge.FindingsIn the present study, we showed that intranasal instillation with a formulation containing TIV and PapMV nanoparticles significantly increase the amount of IgG, IgG2a and IgA in lungs of vaccinated mice as compared to mice that received TIV only. Instillation with the adjuvanted formulation leads to a more robust protection against an influenza infection with a strain that is lethal to mice vaccinated with the TIV.ConclusionsWe demonstrate for the first time that PapMV nanoparticles are an effective and potent mucosal adjuvant for vaccination.

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“…NLRP1, NLRP3, IPAF and AIM2) have been described, each containing a specific danger sensor that mediates recognition of a distinct stimulus or a set of stimuli, including ATP, monosodium urate crystals, the adjuvant alum, as well as various bacterial products45. One event required for inflammasome activation is the generation of reactive oxygen species (ROS), as most known inflammasome stimuli trigger ROS generation and treatment with various ROS scavengers blocks inflammasome activation in response to the agonists26.…”

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confidence: 99%

Surfactin inducing mitochondria-dependent ROS to activate MAPKs, NF-κB and inflammasomes in macrophages for adjuvant activity

Gan

Gao

Zhao

et al. 2016

Sci Rep

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Surfactin, a natural lipopeptide, can be used both as parenteral and non-parenteral adjuvant for eliciting immune response. However, the mechanisms that confer its adjuvant properties have not been fully explored. By staining with NHS-Rhodamine B labeled surfactin and Mito-Tracker Green, we found surfactin could penetrate into macrophages to bind with mitochondria, following induce ROS that could be inhibited by mitochondria-dependent ROS inhibitor. ROS enhanced p38 MAPK and JNK expression, as well their phorsphorylation, following activated NF-κB nuclear translocation in macrophages that was obviously inhibited by mitochondria-dependent ROS inhibitor. However, inhibition of ROS production only weakened p38 MAPK and JNK expression, but not their phosphorylation in macrophages. As a result, surfaction could activate NF-κB to release TNF-α by the mitochondria-dependent ROS signalling pathway. ROS also induced macrophages apoptosis to release endogenous danger signals, following activated inflammasomes of NLRP1, NLRP3, IPAF and AIM2 in vitro and only NLRP1 in vivo, as well caspase-1 and IL-1 in macrophages, which were significantly inhibited by pre-treatment with ROS inhibitors. Collectively, surfactin as a kind of non-pathogen-associated molecular patterns, modulates host innate immunity by multiple signalling pathways, including induction of mitochondria-dependent ROS, activating MAPKs and NF-κB, and inducing cell apoptosis to realease endogenous danger signals for activation of inflammasomes.

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Nanoparticle Adjuvant Sensing by TLR7 Enhances CD8+ T Cell–Mediated Protection from Listeria Monocytogenes Infection

Cited by 56 publications

References 65 publications

In situ vaccination with cowpea mosaic virus nanoparticles suppresses metastatic cancer

In situ vaccination with cowpea mosaic virus nanoparticles suppresses metastatic cancer

PapMV nanoparticles improve mucosal immune responses to the trivalent inactivated flu vaccine

Surfactin inducing mitochondria-dependent ROS to activate MAPKs, NF-κB and inflammasomes in macrophages for adjuvant activity

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