{"doi":"10.1080/10717544.2025.2476144","title":"Development of a single-dose Q fever vaccine with an injectable nanoparticle-loaded hydrogel: effect of sustained co-delivery of antigen and adjuvant","abstract":"Q fever is a zoonotic infectious disease caused by Coxiella burnetii, and there is currently no FDA-approved vaccine for human use. The whole-cell inactivated vaccine Q-VAX, which is only licensed in Australia, has a risk of causing severe adverse reactions, making subunit vaccines a good alternative. However, most subunit antigens are weak immunogens and require two or more immunizations to elicit an adequate level of immunity. We hypothesized that by combining a nanoparticle to co-deliver both a protein antigen and an adjuvant, together with a hydrogel depot for sustained-release kinetics, a single-administration of a nanoparticle-loaded hydrogel vaccine could elicit a strong and durable immune response. We synthesized and characterized a protein nanoparticle (CBU-CpG-E2) that co-delivered the immunodominant protein antigen CBU1910 (CBU) from C. burnetii and the adjuvant CpG1826 (CpG). For sustained release, we examined different mixtures of PLGA-PEG-PLGA (PPP) polymers and identified a PPP solution that was injectable at room temperature, formed a hydrogel at physiological temperature, and continuously released protein for 8 weeks in vivo. Single-dose vaccine formulations were administered to mice, and IgG, IgG1, and IgG2c levels were determined over time. The vaccine combining both the CBU-CpG-E2 nanoparticles and the PPP hydrogel elicited a stronger and more durable humoral immune response than the soluble bolus nanoparticle vaccines (without hydrogel) and the free antigen and free adjuvant-loaded hydrogel vaccines (without nanoparticles), and it yielded a balanced IgG2c/IgG1 response. This study demonstrates the potential advantages of using this modular PPP hydrogel/nanoparticle system to elicit improved immune responses against infectious pathogens.","journal":"Drug Delivery","year":2025,"id":521099,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.952,"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":918562,"name":"A. Gonzaga Ramírez","orcid":"0000-0003-0119-1411","position":1,"is_corresponding":false},{"id":551486,"name":"Jiin Felgner","orcid":null,"position":2,"is_corresponding":false},{"id":918563,"name":"Enya Li","orcid":"0000-0003-2310-7479","position":3,"is_corresponding":false},{"id":832784,"name":"Jenny E. Hernandez‐Davies","orcid":null,"position":4,"is_corresponding":false},{"id":436121,"name":"Anthony E. Gregory","orcid":"0000-0001-5540-1256","position":5,"is_corresponding":false},{"id":104930,"name":"Philip L. Felgner","orcid":"0000-0002-4117-8505","position":6,"is_corresponding":false},{"id":500644,"name":"Ali Mohraz","orcid":"0000-0002-5178-9166","position":7,"is_corresponding":false},{"id":550812,"name":"D. Huw Davies","orcid":"0000-0002-6763-0109","position":8,"is_corresponding":false},{"id":406493,"name":"Szu‐Wen Wang","orcid":"0000-0001-7398-0220","position":9,"is_corresponding":false},{"id":1140665,"name":"Lu Wang","orcid":"0000-0003-2914-6882","position":0,"is_corresponding":true}],"reference_count":100,"raw_metadata":null,"created_at":"2026-07-19T02:49:32.958846Z","pmid":"40314164","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":[]}