{"doi":"10.1101/2024.10.09.617418","title":"A Modular Bacteriophage T4 Nanoparticle Platform Enables Rapid Design of Dual COVID-19-Flu Mucosal Vaccines","abstract":"Abstract A multivalent, rapidly deployable, mucosal vaccine platform is desperately needed to prevent the acquisition and transmission of respiratory infections during epidemics and pandemics. We present one such bacteriophage T4-based platform, and design of dual COVID-19-Flu mucosal vaccines by exploiting its unique architecture. These include: T4’s natural affinity for nasal mucosa, flexible engineering to incorporate multiple antigens, and repeat and symmetric epitope presentation for enhanced B cell responses. Hundreds of SARS-CoV-2 spike trimers and nucleocapsid proteins, and influenza hemagglutinin trimers and M2e peptides, were incorporated into a single phage, creating the highest density nanoparticle presentation yet reported. Intranasal administration of adjuvant-free vaccine induced robust mucosal immunity in mice including, neutralizing antibody and secretory IgA, lung-resident CD4 + /CD8 + T cells, diverse memory B cells, and complete protection against SARS-CoV-2 and influenza challenges. The noninfectious T4 phage offers an extraordinary platform to rapidly design potent mucosal vaccines against emerging bacterial and viral threats.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":505793,"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":0.9517,"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":744307,"name":"Jian Sha","orcid":null,"position":1,"is_corresponding":false},{"id":771401,"name":"Himanshu Batra","orcid":"0000-0002-0203-0591","position":2,"is_corresponding":false},{"id":81413,"name":"Swati Jain","orcid":"0000-0002-8625-8218","position":3,"is_corresponding":false},{"id":687677,"name":"Xiaorong Wu","orcid":"0000-0003-3237-2805","position":4,"is_corresponding":false},{"id":1032064,"name":"Emily Hendrix","orcid":"0000-0002-9248-7738","position":5,"is_corresponding":false},{"id":743717,"name":"Paul B. Kilgore","orcid":"0000-0003-2474-8120","position":6,"is_corresponding":false},{"id":673233,"name":"Keer Sun","orcid":null,"position":7,"is_corresponding":false},{"id":105318,"name":"Kenneth S. Plante","orcid":"0000-0002-7485-3167","position":8,"is_corresponding":false},{"id":105300,"name":"Jessica A. Plante","orcid":"0000-0002-4768-7458","position":9,"is_corresponding":false},{"id":923101,"name":"Jordyn Walker","orcid":null,"position":10,"is_corresponding":false},{"id":1227485,"name":"Pan Tao","orcid":"0009-0002-3203-761X","position":11,"is_corresponding":false},{"id":692721,"name":"Ashok K. Chopra","orcid":"0000-0002-5223-3012","position":12,"is_corresponding":false},{"id":123459,"name":"Venigalla B. Rao","orcid":"0000-0002-0777-6587","position":13,"is_corresponding":false},{"id":447119,"name":"Jingen Zhu","orcid":"0000-0001-7738-7053","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T02:10:47.170978Z","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":[]}