Related Experiment Video
Updated: Jul 15, 2025
Immunostimulatory Agent Evaluation: Lymphoid Tissue Extraction and Injection Route-Dependent Dendritic Cell Activation
Published on: September 16, 2018
Lipid Nanoparticle Delivery Alters the Adjuvanticity of the TLR9 Agonist CpG by Innate Immune Activation in Lymphoid
Zifu Zhong1, Yong Chen1, Kim Deswarte2
1Department of Pharmaceutics, Ghent University, Belgium, Ottergemsesteenweg 460, Gent, 9000, Belgium.
Abstract:
Pharmacological strategies to activate innate immune cells are of great relevance in the context of vaccine design and anticancer immune therapy, to mount broad immune responses able to clear infection and malignant cells. Synthetic CpG oligodeoxynucleotides (CpG-ODNs) are short single-stranded DNA molecules containing unmethylated CpG dinucleotides and a phosphorothioate backbone. Class B CpG ODNs activate robust innate immune responses through a TLR9-dependent NF-κB signaling pathway. This feature is attractive to exploit in the context of vaccine design and cancer immunotherapy. Soluble CpG-ODNs cause hepatic toxicity, which reduces its therapeutic applicability. The formulation of class B CpG ODN1826 in lipid nanoparticles (LNPs) containing an ionizable cationic lipid that complexes CpG through electrostatic interaction is reported. Upon local administration, LNP-formulated CpG drains to lymph nodes and triggers robust innate immune activation. Unformulated, soluble, CpG, by contrast, is unable to induce robust innate activation in draining lymph nodes and is distributed systemically. In a vaccination setting, LNP-formulated CpG, admixed with a protein antigen, induces higher antigen-specific antibody titers and T cell responses than antigen admixed with unformulated soluble CpG.
Insights
Formulating CpG oligodeoxynucleotides (CpG-ODNs) in lipid nanoparticles (LNPs) enhances their ability to activate innate immune cells locally. This LNP formulation improves vaccine efficacy, boosting antibody and T cell responses compared to soluble CpG-ODNs.
Area of Science:
- Immunology
- Nanotechnology
- Pharmacology
Background:
- Synthetic CpG oligodeoxynucleotides (CpG-ODNs) are potent activators of innate immune cells via TLR9 signaling, relevant for vaccines and cancer immunotherapy.
- Unformulated CpG-ODNs can cause hepatic toxicity and lack robust local immune activation upon administration.
- Lipid nanoparticles (LNPs) offer a potential solution for targeted delivery and enhanced immune activation.
Purpose of the Study:
- To investigate the formulation of class B CpG ODN1826 in lipid nanoparticles (LNPs).
- To compare the immune activation and vaccine efficacy of LNP-formulated CpG-ODNs versus soluble CpG-ODNs.
- To assess the potential of LNP-CpG-ODNs for vaccine design and cancer immunotherapy.
Main Methods:
- Formulation of class B CpG ODN1826 into lipid nanoparticles (LNPs) using an ionizable cationic lipid.
- Local administration of LNP-formulated CpG-ODNs and soluble CpG-ODNs in a vaccination setting with a protein antigen.
- Assessment of innate immune activation in draining lymph nodes and systemic distribution.
- Measurement of antigen-specific antibody titers and T cell responses.
Main Results:
- LNP-formulated CpG-ODNs effectively complexed with CpG via electrostatic interaction.
- Local administration of LNP-CpG-ODNs led to robust innate immune activation in draining lymph nodes.
- Soluble CpG-ODNs showed limited local activation and systemic distribution.
- In a vaccination model, LNP-CpG-ODNs admixed with antigen induced significantly higher antigen-specific antibody titers and T cell responses compared to soluble CpG-ODNs.
Conclusions:
- Lipid nanoparticle formulation of CpG-ODNs enhances local innate immune activation and vaccine efficacy.
- LNP-CpG-ODNs represent a promising strategy to overcome the limitations of soluble CpG-ODNs in therapeutic applications.
- This approach holds potential for improving vaccine design and anticancer immune therapy.
More Related Videos
09:51Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
Published on: July 26, 2017
12:53Cell-Free Scaled Production and Adjuvant Addition to a Recombinant Major Outer Membrane Protein from Chlamydia muridarum for Vaccine Development
Published on: March 16, 2022
