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Lipid Nanoparticle Encapsulation Empowers Poly(I:C) to Activate Cytoplasmic RLRs and Thereby Increases Its Adjuvanticity.
Lamoot, Alexander; Jangra, Sonia; Laghlali, Gabriel; Warang, Prajakta; Singh, Gagandeep; Chang, Lauren A; Park, Seok-Chan; Singh, Gagandeep; De Swarte, Kim; Zhong, Zifu; Louage, Benoit; De Lombaerde, Emily; Ye, Tingting; Chen, Yong; Cuadrado-Castano, Sara; Lienenklaus, Stefan; Sanders, Niek N; Lambrecht, Bart N; García-Sastre, Adolfo; Schotsaert, Michael; De Geest, Bruno G.
Affiliation
  • Lamoot A; Department of Pharmaceutics, Ghent University, Ghent, 9000, Belgium.
  • Jangra S; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Laghlali G; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Warang P; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Singh G; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Chang LA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Park SC; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Singh G; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • De Swarte K; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Zhong Z; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Louage B; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • De Lombaerde E; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Ye T; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Chen Y; Biosafety Research Institute, College of Veterinary Medicine, Jeonbuk National University, Iksan, 54596, South Korea.
  • Cuadrado-Castano S; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Lienenklaus S; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Sanders NN; Laboratory of Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent University, Ghent, 9000, Belgium.
  • Lambrecht BN; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, 9000, Belgium.
  • García-Sastre A; Department of Respiratory Medicine, Ghent University Hospital, Ghent, 9000, Belgium.
  • Schotsaert M; Department of Pharmaceutics, Ghent University, Ghent, 9000, Belgium.
  • De Geest BG; Department of Pharmaceutics, Ghent University, Ghent, 9000, Belgium.
Small ; 20(10): e2306892, 2024 Mar.
Article in En | MEDLINE | ID: mdl-37867244
Poly(I:C) is a synthetic analogue of dsRNA capable of activating both TLR3 and RLRs, such as MDA-5 and RIG-I, as pathogen recognition receptors. While poly(I:C) is known to provoke a robust type I IFN, type III IFN, and Th1 cytokine response, its therapeutic use as a vaccine adjuvant is limited due to its vulnerability to nucleases and poor uptake by immune cells. is encapsulated poly(I:C) into lipid nanoparticles (LNPs) containing an ionizable cationic lipid that can electrostatically interact with poly(I:C). LNP-formulated poly(I:C) triggered both lysosomal TLR3 and cytoplasmic RLRs, in vitro and in vivo, whereas poly(I:C) in an unformulated soluble form only triggered endosomal-localized TLR3. Administration of LNP-formulated poly(I:C) in mouse models led to efficient translocation to lymphoid tissue and concurrent innate immune activation following intramuscular (IM) administration, resulting in a significant increase in innate immune activation compared to unformulated soluble poly(I:C). When used as an adjuvant for recombinant full-length SARS-CoV-2 spike protein, LNP-formulated poly(I:C) elicited potent anti-spike antibody titers, surpassing those of unformulated soluble poly(I:C) by orders of magnitude and offered complete protection against a SARS-CoV-2 viral challenge in vivo, and serum from these mice are capable of significantly reducing viral infection in vitro.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Poly I-C / Toll-Like Receptor 3 / Nanoparticles / Spike Glycoprotein, Coronavirus / Liposomes Limits: Animals / Humans Language: En Journal: Small Journal subject: ENGENHARIA BIOMEDICA Year: 2024 Document type: Article Affiliation country: Bélgica Country of publication: Alemania

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Poly I-C / Toll-Like Receptor 3 / Nanoparticles / Spike Glycoprotein, Coronavirus / Liposomes Limits: Animals / Humans Language: En Journal: Small Journal subject: ENGENHARIA BIOMEDICA Year: 2024 Document type: Article Affiliation country: Bélgica Country of publication: Alemania