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Related Concept Videos

Vaccines01:21

Vaccines

Vaccines are among the most effective tools in preventive medicine, designed to prepare the immune system to recognize and combat infectious agents. By introducing antigens—substances that the immune system identifies as foreign—vaccines stimulate an adaptive immune response that leads to immunological memory. This immunological memory enables the body to mount a faster and more effective response upon future exposures to the actual pathogen.Vaccines can be categorized based on the type of...
Vaccinations01:51

Vaccinations

Overview
Modified-Release Drug Delivery Systems: Stimuli-Activated01:30

Modified-Release Drug Delivery Systems: Stimuli-Activated

Stimuli-activated drug delivery systems are designed to release drugs in response to specific physical, chemical, or biological stimuli. These systems often utilize hydrogels—three-dimensional, hydrophilic polymer networks capable of swelling in aqueous environments and retaining significant fluid volumes. Upon exposure to particular stimuli, these hydrogels undergo structural transitions that allow the embedded drug to be released. Due to this adaptive behavior, such systems are also called...

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Whole-animal Imaging and Flow Cytometric Techniques for Analysis of Antigen-specific CD8+ T Cell Responses after Nanoparticle Vaccination
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Inflammasome-activating nanoparticles as modular systems for optimizing vaccine efficacy.

Stacey L Demento1, Stephanie C Eisenbarth, Harald G Foellmer

  • 1Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.

Vaccine
|May 12, 2009
PubMed
Summary

This study introduces novel nanoparticles that activate innate immune pathways for enhanced vaccine design. These lipopolysaccharide-modified nanoparticles effectively stimulate humoral and cellular immunity against model antigens.

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Production of E. coli-expressed Self-Assembling Protein Nanoparticles for Vaccines Requiring Trimeric Epitope Presentation

Published on: August 21, 2019

Area of Science:

  • Immunology
  • Vaccinology
  • Nanotechnology

Background:

  • Innate immune system activation via pattern recognition receptors (PRRs) is crucial for adaptive immunity and adjuvant function.
  • The NLRP3 inflammasome, an intracellular PRR, is activated by classical adjuvants like aluminum hydroxide and saponins.
  • Inflammasome activation requires Toll-like receptor (TLR) and NLRP3 signaling in antigen-presenting cells.

Purpose of the Study:

  • To develop a nanomaterial system that simultaneously delivers antigen and provides dual innate immune signals for optimized vaccine design.
  • To investigate the efficacy of lipopolysaccharide (LPS)-modified nanoparticles in stimulating immune responses.

Main Methods:

  • Constructed nanoparticles from poly(lactic-co-glycolic acid) (PLGA) loaded with antigen and modified with LPS on the surface.
  • Assessed nanoparticle uptake by dendritic cells.
  • Evaluated humoral and cellular immunity in mice immunized with ovalbumin-loaded nanoparticles.
  • Investigated inflammasome activation in wild-type, NLRP3-deficient, and caspase-1-deficient macrophages.
  • Examined the role of endocytosis and lysosomal destabilization in inflammasome activation.
  • Tested the vaccination approach using a recombinant West Nile envelope protein and a West Nile encephalitis mouse model.

Main Results:

  • LPS-modified nanoparticles showed preferential uptake by dendritic cells compared to uncoated nanoparticles.
  • The nanoparticle system elicited potent humoral and cellular immunity against ovalbumin in mice.
  • Macrophages pulsed with LPS-modified nanoparticles produced IL-1beta, indicating inflammasome activation.
  • NLRP3- and caspase-1-deficient macrophages exhibited negligible IL-1beta production.
  • Inhibition of endocytosis and lysosomal destabilization reduced inflammasome activity, suggesting nanoparticle-induced lysosomal rupture.
  • Encapsulation of West Nile envelope protein conferred protection against West Nile encephalitis in mice.

Conclusions:

  • This novel nanoparticle system effectively delivers antigen and stimulates two potent innate immune pathways (TLR and NLRP3 inflammasome).
  • The dual-signal approach represents a significant advancement in simultaneous antigen and adjuvant delivery for vaccine development.
  • This strategy holds promise for creating more effective vaccines against various infectious diseases.