{"doi":"10.1101/2024.10.25.620289","title":"Long-term Immunity of a Microneedle Array Patch of SARS-CoV-2 S1 Protein Subunit Vaccine Irradiated by Gamma Rays in Mice","abstract":"Abstract COVID-19 vaccines effectively prevent symptomatic infection and severe disease, including hospitalization and death. However, unequal vaccine distribution during the pandemic, especially in low- and middle-income countries, has led to the emergence of vaccine-resistant strains. This underscores the need for alternative, safe, and thermostable vaccine platforms, such as dissolved microneedle array patches (MAP) delivering a subunit vaccine, which eliminate the need for cold chain and trained healthcare personnel. This study demonstrates that the SARS-CoV-2 S1 monomer with RS09, a TLR-4 agonist peptide, serves as an optimal protein subunit immunogen. This combination stimulates a stronger S1-specific immune response, resulting in binding to the membrane-bound spike on the cell surface and ACE2-binding inhibition, compared to the monomer S1 alone or trimer S1, regardless of RS09. MAP delivery of the rS1RS09 subunit vaccine elicited higher and longer-lasting immunity compared to conventional intramuscular injection. S1-specific IgG levels remained significantly elevated for up to 70 weeks post-administration. Additionally, different doses of 5, 15, and 45 μ g of MAP vaccines induced robust and sustained Th2-prevalent immune responses, suggesting a dose-sparing effect and inducing significantly high neutralizing antibodies against the Wuhan, Delta, and Omicron variants at 15 and 45 μ g dose. Moreover, gamma irradiation as a terminal sterilization method did not significantly affect immunogenicity, with irradiated vaccines maintaining comparable efficacy to non-irradiated ones. The stability of MAP vaccines was evaluated after long-term storage at room temperature and refrigeration for 19 months, showing minimal protein degradation. Further, after an additional one-month of storage at elevated temperature (42°C), rS1RS09 in both non-irradiated and irradiated MAP degraded less than 3%, while the liquid subunit vaccine degraded over 23%. Overall, these results indicate that gamma irradiation sterilized MAP-rS1RS09 vaccines maintain stability during extended storage without refrigeration, supporting their potential for mass production and widespread use in global vaccination efforts.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":505302,"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":0.9527,"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":1340502,"name":"Muhammad S. Khan","orcid":"0000-0002-6188-7245","position":1,"is_corresponding":false},{"id":1263663,"name":"Juyeop Shin","orcid":null,"position":2,"is_corresponding":false},{"id":228846,"name":"Shaohua Huang","orcid":"0000-0003-2407-949X","position":3,"is_corresponding":false},{"id":1018722,"name":"Alessandro Ferrari","orcid":"0000-0003-2397-7079","position":4,"is_corresponding":false},{"id":286289,"name":"Donghoon Han","orcid":"0000-0003-1870-3006","position":5,"is_corresponding":false},{"id":1263664,"name":"Eun-Jin An","orcid":null,"position":6,"is_corresponding":false},{"id":229925,"name":"Thomas W. Kenniston","orcid":null,"position":7,"is_corresponding":false},{"id":628140,"name":"Irene Cassaniti","orcid":"0000-0002-3385-2088","position":8,"is_corresponding":false},{"id":628158,"name":"Fausto Baldanti","orcid":"0000-0002-3358-8969","position":9,"is_corresponding":false},{"id":1263665,"name":"Dohyeon Jeong","orcid":null,"position":10,"is_corresponding":false},{"id":228853,"name":"Andrea Gambotto","orcid":"0000-0001-8154-7419","position":11,"is_corresponding":false},{"id":1108536,"name":"Eun Kim","orcid":"0000-0001-7963-7722","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:10:43.302033Z","pmid":"39484497","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":[]}