{"doi":"10.1002/smll.202306892","title":"Lipid Nanoparticle Encapsulation Empowers Poly(I:C) to Activate Cytoplasmic RLRs and Thereby Increases Its Adjuvanticity","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.","journal":"Small","year":2023,"id":331816,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9524,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":555491,"name":"Sonia Jangra","orcid":"0000-0002-5671-1632","position":1,"is_corresponding":false},{"id":902109,"name":"Gabriel Laghlali","orcid":"0009-0009-7928-984X","position":2,"is_corresponding":false},{"id":803942,"name":"Prajakta Warang","orcid":"0000-0002-5571-8277","position":3,"is_corresponding":false},{"id":803941,"name":"Gagandeep Singh","orcid":"0000-0003-3260-2631","position":4,"is_corresponding":false},{"id":105591,"name":"Lauren A. Chang","orcid":"0000-0002-3287-3987","position":5,"is_corresponding":false},{"id":1057244,"name":"Seok‐Chan Park","orcid":"0000-0003-2489-2202","position":6,"is_corresponding":false},{"id":1057829,"name":"Kim De Swarte","orcid":null,"position":8,"is_corresponding":false},{"id":304583,"name":"Zifu Zhong","orcid":"0000-0002-5915-1618","position":9,"is_corresponding":false},{"id":1057245,"name":"Benoit Louage","orcid":"0000-0002-6924-1246","position":10,"is_corresponding":false},{"id":1057830,"name":"Emily De Lombaerde","orcid":null,"position":11,"is_corresponding":false},{"id":306410,"name":"Tingting Ye","orcid":null,"position":12,"is_corresponding":false},{"id":684817,"name":"Yong Chen","orcid":"0000-0002-7029-6201","position":13,"is_corresponding":false},{"id":855986,"name":"Sara Cuadrado‐Castano","orcid":"0000-0002-9400-746X","position":14,"is_corresponding":false},{"id":560563,"name":"Stefan Lienenklaus","orcid":"0000-0003-4790-3445","position":15,"is_corresponding":false},{"id":474972,"name":"Niek N. Sanders","orcid":"0000-0003-4585-0343","position":16,"is_corresponding":false},{"id":80095,"name":"Bart N. Lambrecht","orcid":"0000-0003-4376-6834","position":17,"is_corresponding":false},{"id":1489,"name":"Adolfo Garcı́a-Sastre","orcid":"0000-0002-6551-1827","position":18,"is_corresponding":false},{"id":107923,"name":"Michael Schotsaert","orcid":"0000-0003-3156-3132","position":19,"is_corresponding":false},{"id":304584,"name":"Bruno G. De Geest","orcid":"0000-0001-9826-6170","position":20,"is_corresponding":false},{"id":685705,"name":"Alexander Lamoot","orcid":null,"position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T01:09:25.015646Z","pmid":"37867244","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}