{"doi":"10.1002/advs.202402792","title":"A Dual‐Adjuvanted Parenteral‐Intranasal Subunit Nanovaccine generates Robust Systemic and Mucosal Immunity Against SARS‐CoV‐2 in Mice","abstract":"Existing parenteral SARS-CoV-2 vaccines produce only limited mucosal responses, essential for reducing transmission and achieving sterilizing immunity. Appropriately designed mucosal boosters can overcome the shortcomings of parenteral vaccines and enhance pre-existing systemic immunity. Here, a new protein subunit nanovaccine is developed by utilizing dual-adjuvanted (RIG-I: PUUC RNA and TLR-9: CpG DNA) polysaccharide-amino acid-lipid nanoparticles (PAL-NPs) along with SARS-CoV-2 S1 trimer protein, that can be delivered both intramuscularly (IM) and intranasally (IN) to generate balanced mucosal-systemic SARS-CoV-2 immunity. Mice receiving IM-Prime PUUC+CpG PAL subunit nanovaccine, followed by an IN-Boost, developed high levels of IgA, IgG, and cellular immunity in the lungs and showed robust systemic humoral immunity. Interestingly, as a purely intranasal subunit vaccine (IN-Prime/IN-Boost), PUUC+CpG PAL-NPs induced stronger lung-specific T cell immunity than IM-Prime/IN-Boost, and a comparable IgA and neutralizing antibodies, although with a lower systemic antibody response, indicating that a fully mucosal delivery route for SARS-CoV-2 vaccination may also be feasible. The data suggest that PUUC+CpG PAL subunit nanovaccine is a promising candidate for generating SARS-CoV-2 specific mucosal immunity.","journal":"Advanced Science","year":2024,"id":445629,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1262468,"name":"Zhengying Wang","orcid":null,"position":1,"is_corresponding":false},{"id":881824,"name":"Angela Jimenez","orcid":"0000-0002-2490-4122","position":2,"is_corresponding":false},{"id":1081725,"name":"Eshant Bhatia","orcid":"0000-0002-4451-9889","position":3,"is_corresponding":false},{"id":881822,"name":"Ritika Jain","orcid":"0000-0003-4530-7578","position":4,"is_corresponding":false},{"id":882642,"name":"Alexander Beach","orcid":null,"position":5,"is_corresponding":false},{"id":928238,"name":"Drishti Maniar","orcid":null,"position":6,"is_corresponding":false},{"id":576433,"name":"Justin Hosten","orcid":null,"position":7,"is_corresponding":false},{"id":789296,"name":"Laura O’Farrell","orcid":null,"position":8,"is_corresponding":false},{"id":474668,"name":"Casey E. Vantucci","orcid":"0000-0002-2587-9555","position":9,"is_corresponding":false},{"id":505286,"name":"David J. Hur","orcid":"0000-0002-5604-3670","position":10,"is_corresponding":false},{"id":882643,"name":"Richard Noel","orcid":null,"position":11,"is_corresponding":false},{"id":1262469,"name":"Rachel Rinqguist","orcid":null,"position":12,"is_corresponding":false},{"id":881823,"name":"Clinton Smith","orcid":"0009-0005-5269-3472","position":13,"is_corresponding":false},{"id":446473,"name":"Miguel Armenta Ochoa","orcid":null,"position":14,"is_corresponding":false},{"id":474672,"name":"Krishnendu Roy","orcid":"0000-0002-9972-0950","position":15,"is_corresponding":false},{"id":745732,"name":"Bhawana Pandey","orcid":"0000-0003-4090-2618","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-19T02:01:46.243344Z","pmid":"39352717","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":[]}