{"doi":"10.17615/041d-s909","title":"Inclusion of Flagellin during Vaccination against Influenza Enhances Recall Responses in Nonhuman Primate Neonates","abstract":"ABSTRACT Influenza virus can cause life-threatening infections in neonates and young infants. Although vaccination is a major countermeasure against influenza, current vaccines are not approved for use in infants less than 6 months of age, in part due to the weak immune response following vaccination. Thus, there is a strong need to develop new vaccines with improved efficacy for this vulnerable population. To address this issue, we established a neonatal African green monkey (AGM) nonhuman primate model that could be used to identify effective influenza vaccine approaches for use in young infants. We assessed the ability of flagellin, a Toll-like receptor 5 (TLR5) agonist, to serve as an effective adjuvant in this at-risk population. Four- to 6-day-old AGMs were primed and boosted with inactivated PR8 influenza virus (IPR8) adjuvanted with either wild-type flagellin or inactive flagellin with a mutation at position 229 (m229), the latter of which is incapable of signaling through TLR5. Increased IgG responses were observed following a boost, as well as at early times after challenge, in infants vaccinated with flagellin-adjuvanted IPR8. Inclusion of flagellin during vaccination also resulted in a significantly increased number of influenza virus-specific T cells following challenge compared to the number in infants vaccinated with the m229 adjuvant. Finally, following challenge infants vaccinated with IPR8 plus flagellin exhibited a reduced pathology in the lungs compared to that in infants that received IPR8 plus m229. This study provides the first evidence of flagellin-mediated enhancement of vaccine responses in nonhuman primate neonates. IMPORTANCE Young infants are particularly susceptible to severe disease as a result of influenza virus infection. Compounding this is the lack of effective vaccines for use in this vulnerable population. Here we describe a vaccine approach that results in improved immune responses and protection in young infants. Incorporation of flagellin during vaccination resulted in increased antibody and T cell responses together with reduced disease following virus infection. These results suggest that flagellin may serve as an effective adjuvant for vaccines targeted to this vulnerable population.","journal":"UNC Libraries","year":2020,"id":138302,"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":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":275696,"name":"Sarah L. Hayward","orcid":"0000-0001-7052-5556","position":1,"is_corresponding":false},{"id":326697,"name":"Matthew J. Jorgensen","orcid":"0000-0002-0977-6425","position":2,"is_corresponding":false},{"id":593507,"name":"Lance K. Blevins","orcid":"0000-0002-8911-8843","position":3,"is_corresponding":false},{"id":43418,"name":"Ralph B. D’Agostino","orcid":"0000-0002-3550-8395","position":4,"is_corresponding":false},{"id":600276,"name":"Steven B. Mizel","orcid":null,"position":5,"is_corresponding":false},{"id":599758,"name":"Jongrok Kim","orcid":"0000-0003-1519-3274","position":6,"is_corresponding":false},{"id":322701,"name":"Martha A. Alexander‐Miller","orcid":"0000-0003-3455-0716","position":7,"is_corresponding":false},{"id":599759,"name":"Griffith D. Parks","orcid":"0000-0002-7365-0093","position":8,"is_corresponding":false},{"id":600277,"name":"S. Tyler Aycock","orcid":null,"position":9,"is_corresponding":false},{"id":599760,"name":"Nancy D. Kock","orcid":"0000-0002-7167-5473","position":10,"is_corresponding":false},{"id":444170,"name":"Kristina De Paris","orcid":"0000-0001-5199-3004","position":11,"is_corresponding":false},{"id":173912,"name":"Beth C. Holbrook","orcid":"0000-0001-6026-695X","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:17:02.849477Z","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":[]}