{"doi":"10.1016/j.jconrel.2025.114054","title":"An intranasally- and intramuscularly-deliverable nanostructured lipid carrier-replicon RNA vaccine drives protective systemic and mucosal immunity","abstract":null,"journal":"Journal of Controlled Release","year":2025,"id":628432,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1457671,"name":"Devin S. Brandt","orcid":null,"position":1,"is_corresponding":false},{"id":554022,"name":"Madeleine F. Jennewein","orcid":"0000-0001-6633-7413","position":2,"is_corresponding":false},{"id":985467,"name":"Jasneet Singh","orcid":"0000-0001-6494-7816","position":3,"is_corresponding":false},{"id":986020,"name":"Samuel Beaver","orcid":null,"position":4,"is_corresponding":false},{"id":1627057,"name":"Matthew R. Ykema","orcid":null,"position":5,"is_corresponding":false},{"id":1453186,"name":"Christopher Press","orcid":null,"position":6,"is_corresponding":false},{"id":1225028,"name":"Eduard Melief","orcid":"0000-0002-2464-8966","position":7,"is_corresponding":false},{"id":986022,"name":"Julie Bakken","orcid":null,"position":8,"is_corresponding":false},{"id":1453187,"name":"Pauline Fusco","orcid":null,"position":9,"is_corresponding":false},{"id":1627061,"name":"Ethan Lo","orcid":null,"position":10,"is_corresponding":false},{"id":986021,"name":"Peter Battisti","orcid":null,"position":11,"is_corresponding":false},{"id":986024,"name":"Noah Cross","orcid":null,"position":12,"is_corresponding":false},{"id":336734,"name":"Darshan N. Kasal","orcid":"0000-0003-2718-7971","position":13,"is_corresponding":false},{"id":1627064,"name":"Airn Tolnay Hartwig","orcid":null,"position":14,"is_corresponding":false},{"id":299039,"name":"Corey Casper","orcid":"0000-0002-3609-661X","position":15,"is_corresponding":false},{"id":228136,"name":"Richard A. Bowen","orcid":"0000-0002-7576-2881","position":16,"is_corresponding":false},{"id":321242,"name":"Alana Gerhardt","orcid":"0000-0001-6753-7134","position":17,"is_corresponding":false},{"id":495328,"name":"Emily A. Voigt","orcid":"0000-0001-5177-4063","position":18,"is_corresponding":false},{"id":1407267,"name":"Wynton D. McClary","orcid":"0000-0003-3210-4747","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"An intranasally- and intramuscularly-deliverable nanostructured lipid carrier-replicon RNA vaccine drives protective systemic and mucosal immunity","abstract":"A nucleic acid vaccine platform that could be flexibly administered either intranasally or intramuscularly could be a valuable new tool for epidemic and pandemic response, combining rapid antigen adaptability with optimal induction of systemic and/or mucosal immune responses most appropriate for a particular pathogen. However, such RNA vaccines have not yet been developed. We have developed and optimized dual intranasal and intramuscular deliverability of a proof-of-concept replicon vaccine expressing an H5 influenza antigen that uses a nanostructured lipid carrier (NLC) delivery system. A relationship was established between the RNA:NLC loading ratio, vaccine particle charge, RNA delivery to cells, and finally intranasal vaccine immunogenicity, allowing for identification of a single vaccine formulation that can be effectively administered via both intramuscular and intranasal routes. The vaccine induced systemic immunity when dosed intramuscularly or intranasally in an immunocompetent mouse model, whereas intranasal dosing uniquely stimulated a strong mucosal immune response. Moreover, a mixed intramuscular/intranasal dosing strategy stimulated a balanced systemic and mucosal immune response. Finally, we demonstrated the protective efficacy of an intranasally- and intramuscularly/intranasally-delivered H5 replicon-NLC vaccine against morbidity and mortality in a lethal H5N1 influenza challenge ferret model.","is_dataset_classified":null,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40695376","pmcid":null,"openalex_id":"https://openalex.org/W4412495759","authors":[],"funders":[{"funder_name":"Biomedical Advanced Research and Development Authority","grant_id":"75A50121C00087","title":null},{"funder_name":"Joint Program Executive Office for Chemical Biological Radiological and Nuclear Defense","grant_id":"MCDC2204\\u2010001","title":null},{"funder_name":"U.S. Department of Health and Human Services","grant_id":"","title":null},{"funder_name":"U.S. Department of Defense","grant_id":"","title":null},{"funder_name":"Administration for Strategic Preparedness and Response","grant_id":"","title":null}],"total_grants":5,"fwci":3.2563,"citation_percentile":0.92551378,"influential_citations":0,"citation_trend":[{"year":2026,"count":8}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1016/j.jconrel.2025.114054","host_type":"journal"},{"url":"https://doi.org/10.1016/j.jconrel.2025.114054","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0168365925006765?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0168365925006765?httpAccept=text/plain","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40695376","host_type":"repository"}],"fields_of_study":["RNA Interference and Gene Delivery","Immunotherapy and Immune Responses","SARS-CoV-2 and COVID-19 Research","Animals","Administration, Intranasal","Immunity, Mucosal","Injections, Intramuscular","Influenza Vaccines","Female","Lipids","Mice, Inbred BALB C","Orthomyxoviridae Infections","Nanostructures","Mice","Influenza A Virus, H5N1 Subtype","Drug Carriers","Replicon"],"mesh_terms":["Administration, Intranasal","Animals","Drug Carriers","Female","Influenza Vaccines","Injections, Intramuscular","Lipids","Mice, Inbred BALB C","Orthomyxoviridae Infections","Replicon","Immunity, Mucosal","Nanostructures","Mice","Influenza A Virus, H5N1 Subtype"],"keywords":["Nasal administration","Replicon","Deliverable","Immunity","Virology","Mucosal immunity","Medicine","Microbiology","Immunology","Chemistry","Biology","Immune system","Biochemistry","Pandemic influenza","Nanostructured Lipid Carrier","Intranasal Administration","Heterologous Dosing","Replicon Vaccines"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Zero hunger"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T13:31:20.954537Z","pmid":null,"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":[]}