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journal article·2024-03Open access

Lipid Nanoparticle Encapsulation Empowers Poly(I:C) to Activate Cytoplasmic RLRs and Thereby Increases Its Adjuvanticity

Alexander Lamoot, Sonia Jangra, Gabriel Laghlali, Prajakta Warang, Gagandeep Singh, Lauren A. Chang, Seok‐Chan Park, Gagandeep Singh, Kim De Swarte, Zifu Zhong, Benoit Louage, Emily De Lombaerde, Tingting Ye, Yong Chen, Sara Cuadrado‐Castano, Stefan Lienenklaus, Niek N. Sanders, Bart N. Lambrecht, Adolfo García‐Sastre, Michael Schotsaert, Bruno G. De Geest

Small· Volume 20· Issue 10
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Source abstract

Abstract

Abstract 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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Research context

Nanomaterials

OpenAlex topics: Immune Response and Inflammation · Immune Cell Function and Interaction · Immunotherapy and Immune Responses

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Pharmaceutics Ghent University Ghent 9000 Belgium

Department of Microbiology Icahn School of Medicine at Mount Sinai New York NY 10029 USA

Global Health and Emerging Pathogens Institute Icahn School of Medicine at Mount Sinai New York NY 10029 USA

Graduate School of Biomedical Sciences Icahn School of Medicine at Mount Sinai New York NY 10029 USA

Biosafety Research Institute College of Veterinary Medicine Jeonbuk National University Iksan 54596 South Korea

Laboratory of Mucosal Immunology VIB‐UGent Center for Inflammation Research Ghent University Ghent 9000 Belgium

Department of Internal Medicine and Pediatrics Faculty of Medicine and Health Sciences Ghent University Ghent 9000 Belgium

Department of Respiratory Medicine Ghent University Hospital Ghent 9000 Belgium

Icahn Genomics Institute Icahn School of Medicine at Mount Sinai New York NY 10029 USA

Lipschultz Precision Immunology Institute Icahn School of Medicine at Mount Sinai New York NY 10029 USA

Institute for Laboratory Animal Science and Institute of Immunology Hannover Medical School 30625 Hannover Germany

Laboratory of Gene Therapy Ghent University Merelbeke 9820 Belgium

Department of Medicine Division of Infectious Diseases Icahn School of Medicine at Mount Sinai New York NY 10029 USA

The Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York NY 10029 USA

Department of Pathology Molecular and Cell‐Based Medicine Icahn School of Medicine at Mount Sinai New York NY 10029 USA

Funding

National Institute of Allergy and Infectious Diseases · European Research Council · Korea Health Industry Development Institute

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