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Lipid nanoparticle delivery alters the adjuvanticity of the TLR9 agonist CpG by innate immune activation in lymphoid tissue

Zifu Zhong (UGent) , Yong Chen (UGent) , Kim Deswarte (UGent) , Heleen Lauwers (UGent) , Emily De Lombaerde (UGent) , Xiaole Cui (UGent) , Simon Van Herck (UGent) , Tingting Ye (UGent) , Mark Gontsarik (UGent) , Stefan Lienenklaus, et al.
(2023) ADVANCED HEALTHCARE MATERIALS. 12(32).
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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-kappa B 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.
Keywords
Pharmaceutical Science, Biomedical Engineering, Biomaterials, CpG ODN, immune therapy, lipid nanoparticles, TLR9, vaccine adjuvants, 1ST-LINE TREATMENT, RECOGNITION, RECEPTORS, CELLS, MODEL, DNA

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Citation

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MLA
Zhong, Zifu, et al. “Lipid Nanoparticle Delivery Alters the Adjuvanticity of the TLR9 Agonist CpG by Innate Immune Activation in Lymphoid Tissue.” ADVANCED HEALTHCARE MATERIALS, vol. 12, no. 32, 2023, doi:10.1002/adhm.202301687.
APA
Zhong, Z., Chen, Y., Deswarte, K., Lauwers, H., De Lombaerde, E., Cui, X., … De Geest, B. (2023). Lipid nanoparticle delivery alters the adjuvanticity of the TLR9 agonist CpG by innate immune activation in lymphoid tissue. ADVANCED HEALTHCARE MATERIALS, 12(32). https://doi.org/10.1002/adhm.202301687
Chicago author-date
Zhong, Zifu, Yong Chen, Kim Deswarte, Heleen Lauwers, Emily De Lombaerde, Xiaole Cui, Simon Van Herck, et al. 2023. “Lipid Nanoparticle Delivery Alters the Adjuvanticity of the TLR9 Agonist CpG by Innate Immune Activation in Lymphoid Tissue.” ADVANCED HEALTHCARE MATERIALS 12 (32). https://doi.org/10.1002/adhm.202301687.
Chicago author-date (all authors)
Zhong, Zifu, Yong Chen, Kim Deswarte, Heleen Lauwers, Emily De Lombaerde, Xiaole Cui, Simon Van Herck, Tingting Ye, Mark Gontsarik, Stefan Lienenklaus, Niek Sanders, Bart Lambrecht, Stefaan De Koker, and Bruno De Geest. 2023. “Lipid Nanoparticle Delivery Alters the Adjuvanticity of the TLR9 Agonist CpG by Innate Immune Activation in Lymphoid Tissue.” ADVANCED HEALTHCARE MATERIALS 12 (32). doi:10.1002/adhm.202301687.
Vancouver
1.
Zhong Z, Chen Y, Deswarte K, Lauwers H, De Lombaerde E, Cui X, et al. Lipid nanoparticle delivery alters the adjuvanticity of the TLR9 agonist CpG by innate immune activation in lymphoid tissue. ADVANCED HEALTHCARE MATERIALS. 2023;12(32).
IEEE
[1]
Z. Zhong et al., “Lipid nanoparticle delivery alters the adjuvanticity of the TLR9 agonist CpG by innate immune activation in lymphoid tissue,” ADVANCED HEALTHCARE MATERIALS, vol. 12, no. 32, 2023.
@article{01HMB3J8RDAHVDEFAY7FHH7HA6,
  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-kappa B 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.}},
  articleno    = {{2301687}},
  author       = {{Zhong, Zifu and Chen, Yong and Deswarte, Kim and Lauwers, Heleen and De Lombaerde, Emily and Cui, Xiaole and Van Herck, Simon and Ye, Tingting and Gontsarik, Mark and Lienenklaus, Stefan and Sanders, Niek and Lambrecht, Bart and De Koker, Stefaan and De Geest, Bruno}},
  issn         = {{2192-2640}},
  journal      = {{ADVANCED HEALTHCARE MATERIALS}},
  keywords     = {{Pharmaceutical Science,Biomedical Engineering,Biomaterials,CpG ODN,immune therapy,lipid nanoparticles,TLR9,vaccine adjuvants,1ST-LINE TREATMENT,RECOGNITION,RECEPTORS,CELLS,MODEL,DNA}},
  language     = {{eng}},
  number       = {{32}},
  pages        = {{13}},
  title        = {{Lipid nanoparticle delivery alters the adjuvanticity of the TLR9 agonist CpG by innate immune activation in lymphoid tissue}},
  url          = {{http://doi.org/10.1002/adhm.202301687}},
  volume       = {{12}},
  year         = {{2023}},
}
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