{"doi":"10.1101/2025.07.16.665134","title":"Controlled Release of Poly(U) via Acetalated Dextran Microparticles for Enhanced Vaccine Adjuvant Delivery","abstract":"Diverse drug delivery systems are needed to address challenges in delivering novel vaccine components and enhancing their efficacy. Poly(U) is a single-stranded RNA composed of uracil repeats that acts as a toll-like receptor (TLR) 7/8 agonist, stimulating the innate immune system. However, poly(U) is susceptible to ribonuclease degradation without a delivery carrier, and its negative charge hinders cellular uptake. Encapsulation in acetalated dextran (Ace-DEX), a pH-sensitive, biodegradable polymer, addresses these challenges. This study encapsulated poly(U) into Ace-DEX Microparticles (MPs) with either spherical (smooth MPs) or collapsed-surface (wrinkled MPs) via spray-drying. It was hypothesized that the different morphologies of MPs would influence the vaccine efficacy after in vitro and in vivo models. Smooth poly(U) MPs had a higher percent viability and cytokine response in dendritic cells (DCs) than wrinkled poly(U) MPs. Moreover, mice vaccinated with smooth poly(U) MPs + ovalbumin (OVA) showed enhanced IL-2 production and IFN-γ in response to OVA peptide and MHC-I immunodominant peptide restimulation, respectively, compared to wrinkled poly(U) MPs. However, mice vaccinated with wrinkled poly(U) MPs + OVA significantly increased B-cell and germinal center B-cell frequencies compared to mice vaccinated with phosphate buffered saline (PBS) whereas mice vaccinated with smooth poly(U) MPs + OVA did not. Overall, these findings suggest that smooth poly(U) MPs modulated dendritic cells and T-cells, and wrinkled poly(U) MPs modulated B-cells. Understanding how morphology influences these cell types will aid in optimizing future vaccine systems for more specific cellular targeting.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":570598,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":940911,"name":"Nicole Rose Lukesh","orcid":"0000-0003-4030-1505","position":1,"is_corresponding":false},{"id":854246,"name":"Erik S. Pena","orcid":"0000-0002-9204-5155","position":2,"is_corresponding":false},{"id":1025764,"name":"Ryan N. Woodring","orcid":"0000-0002-7818-8387","position":3,"is_corresponding":false},{"id":1393035,"name":"Sophie E. Mendell","orcid":"0000-0002-8700-1385","position":4,"is_corresponding":false},{"id":1252477,"name":"Connor T. Murphy","orcid":"0009-0009-2533-5804","position":5,"is_corresponding":false},{"id":1110973,"name":"Grace L. Williamson","orcid":"0000-0003-4711-1130","position":6,"is_corresponding":false},{"id":1476171,"name":"Kierstin A. Clark","orcid":"0009-0006-3502-977X","position":7,"is_corresponding":false},{"id":1320879,"name":"A. López","orcid":"0000-0002-3085-4256","position":8,"is_corresponding":false},{"id":419622,"name":"Eric M. Bachelder","orcid":"0000-0002-8572-888X","position":9,"is_corresponding":false},{"id":419623,"name":"Kristy M. Ainslie","orcid":"0000-0002-1820-8382","position":10,"is_corresponding":false},{"id":1476512,"name":"Sokny Ly","orcid":null,"position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:57:11.713851Z","pmid":"40777285","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":[]}