Non-canonical inflammasome activation mediates the adjuvanticity of nanoparticles

Muñoz‐Wolf, Natalia; Ward, Ross W.; Hearnden, Claire H.; Sharp, Fiona A.; Geoghegan, Joan A.; O’Grady, Katie; McEntee, Craig P.; Shanahan, Katharine A.; Guy, Coralie; Bowie, Andrew; Campbell, Matthew; Roces, Carla B.; Anderluzzi, Giulia; Webb, Cameron; Perrie, Yvonne; Creagh, Emma M.; Lavelle, Ed C.

doi:10.1016/j.xcrm.2022.100899

Cited by 19 publications

(16 citation statements)

References 64 publications

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“…For example, ferritin-based vaccines have recently emerged as vaccine candidates for pathogens such as Influenza, Epstein-Barr, and SARS-CoV-2 viruses due to the ability to self-assemble into a virus-like particle with comparable size and structure to these pathogens, with the added advantage of surface antigen display [12]. Although it is considered unlikely that synthetic polymeric nanoparticles directly engage specific pathogen or damage-sensing receptors, these adjuvants may promote immune responses via the induction of cell stress or immunogenic cell death [13]. The capacity of particles to promote (or suppress) immune responses is associated with specific tunable physicochemical properties of the adjuvant, including diameter, charge, and surface properties.…”

Section: Polymeric Particulate Adjuvantsmentioning

confidence: 99%

“…In addition to the previously established mechanisms by which polymeric particles can activate DCs to enhance cellular immunity, the induction of cell stress or death by polymeric particles can also trigger this type of response through the release of damage‐associated molecular patterns and activation of danger receptors [13]. There have been a wide range of regulated cell death modalities described, the most prominent forms being apoptosis, necroptosis, and pyroptosis, these regulated cell death forms may also fall into the bracket of immunogenic cell death (ICD) if certain criteria are fulfilled, providing antigenicity and adjuvanticity, resulting in the capacity to mount adaptive immune responses to antigens expressed by the dying cell.…”

Section: Main Textmentioning

confidence: 99%

“…Polymeric nanoparticles were recently demonstrated to activate the noncanonical inflammasome (caspase 11 and GSDMD formation) leading to enhanced CD8 + T cell and Th1‐biased responses. Furthermore, this response was restricted to particles of 50–60 nm size in diameter [55]. The enhancement of this type of immune response is crucial for prophylactic vaccines but also for therapeutic vaccines against cancer.…”

Section: Main Textmentioning

confidence: 99%

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Rational design of polymer‐based particulate vaccine adjuvants

Huete‐Carrasco,

Lynch,

Ward

et al. 2023

Eur J Immunol

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Vaccination is considered one of the major milestones in modern medicine, facilitating the control and eradication of life‐threatening infectious diseases. Vaccine adjuvants are a key component of many vaccines, serving to steer antigen‐specific immune responses and increase their magnitude. Despite major advances in the field of adjuvant research over recent decades, our understanding of their mechanism of action remains incomplete. This hinders our capacity to further improve these adjuvant technologies, so addressing how adjuvants induce and control the induction of innate and adaptive immunity is a priority. Investigating how adjuvant physicochemical properties, such as size and charge, exert immunomodulatory effects can provide valuable insights and serve as the foundation for the rational design of vaccine adjuvants. Most clinically applied adjuvants are particulate in nature and polymeric particulate adjuvants present advantages due to stability, biocompatibility profiles, and flexibility in terms of formulation. These properties can impact on antigen release kinetics and biodistribution, cellular uptake and targeting, and drainage to the lymphatics, consequently dictating the induction of innate, cellular, and humoral adaptive immunity. A current focus is to apply rational design principles to the development of adjuvants capable of eliciting robust cellular immune responses including CD8+ cytotoxic T‐cell and Th1‐biased CD4+ T‐cell responses, which are required for vaccines against intracellular pathogens and cancer. This review highlights recent advances in our understanding of how particulate adjuvants, especially polymer‐based particulates, modulate immune responses and how this can be used as a guide for improved adjuvant design.

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Section: Polymeric Particulate Adjuvantsmentioning

confidence: 99%

Section: Main Textmentioning

confidence: 99%

Section: Main Textmentioning

confidence: 99%

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Rational design of polymer‐based particulate vaccine adjuvants

Huete‐Carrasco,

Lynch,

Ward

et al. 2023

Eur J Immunol

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“…To improve drug absorption and enrichment, a variety of nanocarriers have been employed recently, including nanoparticles, nanofiber, nanosheets, and nanoemulsions. − Among them, nanoemulsion (NE) is a promising nanocarrier system with good stability and skin penetration, with a particle size between 10 and 100 nm . A nanoemulsion system has been developed not only to enhance percutaneous absorption but also to allow the drug to target the skin or even its substructure, which has been widely used in the loading of insoluble drugs and Chinese herbal extracts in recent years. − However, the low viscosity of NE makes it difficult to apply it to the skin.…”

Section: Introductionmentioning

confidence: 99%

Preparation of Compound Salvia miltiorrhiza–Blumea balsamifera Nanoemulsion Gel and Its Effect on Hypertrophic Scars in the Rabbit Ear Model

Chen,

Wang,

Gong

et al. 2024

Mol. Pharmaceutics

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Hypertrophic scars (HS) still remain an urgent challenge in the medical community. Traditional Chinese medicine (TCM) has unique advantages in the treatment of HS. However, due to the natural barrier of the skin, it is difficult for the natural active components of TCM to more effectively penetrate the skin and exert therapeutic effects. Therefore, the development of an efficient drug delivery system to facilitate enhanced transdermal absorption of TCM becomes imperative for its clinical application. In this study, we designed a compound Salvia miltiorrhiza−Blumea balsamifera nanoemulsion gel (CSB-NEG) and investigated its therapeutic effects on rabbit HS models. The prescription of CSB-NEG was optimized by single-factor, pseudoternary phase diagram, and central composite design experiments. The results showed that the average particle size and PDI of the optimized CSB-NE were 46.0 ± 0.2 nm and 0.222 ± 0.004, respectively, and the encapsulation efficiency of total phenolic acid was 93.37 ± 2.56%. CSB-NEG demonstrated excellent stability and skin permeation in vitro and displayed a significantly enhanced ability to inhibit scar formation compared to the CSB physical mixture in vivo. After 3 weeks of CSB-NEG treatment, the scar appeared to be flat, pink, and flexible. Furthermore, this treatment also resulted in a decrease in the levels of the collagen I/III ratio and TGF-β 1 and Smad2 proteins while simultaneously promoting the growth and remodeling of microvessels. These findings suggest that CSB-NEG has the potential to effectively address the barrier properties of the skin and provide therapeutic benefits for HS, offering a new perspective for the prevention and treatment of HS.

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“…15 Furthermore, certain types of PLGA have been proven a potent adjuvant through the activation of the noncanonical inflammasome mechanisms leading to production of proinflammatory cytokines, inducing cell-mediated immunity and humoral immunity. 16 Precise tailoring of particle size to 50−60 nm has been proven key toward this objective. 16 Moreover, the addition of polyethylene glycol (PEG) to PLGA NPs (PLGA-PEG NPs) impedes their rapid elimination, thus increasing their blood circulation half-life which is essential for selective immune cells targeting.…”

Section: Introductionmentioning

confidence: 99%

Targeted and Self-Adjuvated Nanoglycovaccine Candidate for Cancer Immunotherapy

Freitas,

Ferreira,

Miranda

et al. 2024

ACS Nano

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Advanced-stage solid primary tumors and metastases often express mucin 16 (MUC16), carrying immature glycans such as the Tn antigen, resulting in specific glycoproteoforms not found in healthy human tissues. This presents a valuable approach for designing targeted therapeutics, including cancer glycovaccines, which could potentially promote antigen recognition and foster the immune response to control disease spread and prevent relapse. In this study, we describe an adjuvant-free poly(lactic-co-glycolic acid) (PLGA)based nanoglycoantigen delivery approach that outperforms conventional methods by eliminating the need for protein carriers while exhibiting targeted and adjuvant properties. To achieve this, we synthesized a library of MUC16-Tn glycoepitopes through single-pot enzymatic glycosylation, which were then stably engrafted onto the surface of PLGA nanoparticles, generating multivalent constructs that better represent cancer molecular heterogeneity. These glycoconstructs demonstrated affinity for Macrophage Galactose-type Lectin (MGL) receptor, known to be highly expressed by immature antigen-presenting cells, enabling precise targeting of immune cells. Moreover, the glycopeptide-grafted nanovaccine candidate displayed minimal cytotoxicity and induced the activation of dendritic cells in vitro, even in the absence of an adjuvant. In vivo, the formulated nanovaccine candidate was also nontoxic and elicited the production of IgG specifically targeting MUC16 and MUC16-Tn glycoproteoforms in cancer cells and tumors, offering potential for precise cancer targeting, including targeted immunotherapies.

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Non-canonical inflammasome activation mediates the adjuvanticity of nanoparticles

Cited by 19 publications

References 64 publications

Rational design of polymer‐based particulate vaccine adjuvants

Rational design of polymer‐based particulate vaccine adjuvants

Preparation of Compound Salvia miltiorrhiza–Blumea balsamifera Nanoemulsion Gel and Its Effect on Hypertrophic Scars in the Rabbit Ear Model

Targeted and Self-Adjuvated Nanoglycovaccine Candidate for Cancer Immunotherapy

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