{"doi":"10.1128/spectrum.00078-22","title":"Mutation L319Q in the PB1 Polymerase Subunit Improves Attenuation of a Candidate Live-Attenuated Influenza A Virus Vaccine","abstract":"Vaccination represents the most effective strategy to reduce the impact of seasonal IAV infections. Although LAIV are superior in inducing protection and sterilizing immunity, they are not recommended for many individuals who are at high risk for severe disease. Thus, development of safer and more effective LAIV are needed. A concern with the current MDV used to generate the U.S.-licensed LAIV is that it is based on a virus isolated in 1960. Moreover, mutations that confer the temperature-sensitive, cold-adapted, and attenuated phenotype of the U.S. MDV resulted in low level of attenuation in the contemporary pandemic A/California/04/09 H1N1 (pH1N1). Here, we show that introduction of PB1 L319Q substitution, alone or in combination with the U.S. MDV mutations, resulted in pH1N1 attenuation. These findings support the development of a novel LAIV MDV based on a contemporary pH1N1 strain as a medical countermeasure against currently circulating H1N1 IAV.","journal":"Microbiology Spectrum","year":2022,"id":282277,"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":0.9555,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":456499,"name":"John Steel","orcid":"0000-0003-1217-0990","position":1,"is_corresponding":false},{"id":103709,"name":"Wen‐Chun Liu","orcid":"0000-0003-0344-4371","position":2,"is_corresponding":false},{"id":232940,"name":"Anice C. Lowen","orcid":"0000-0002-9829-112X","position":3,"is_corresponding":false},{"id":182092,"name":"Laura Rodríguez","orcid":null,"position":4,"is_corresponding":false},{"id":277648,"name":"Kevin Chiem","orcid":"0000-0002-3892-5944","position":5,"is_corresponding":false},{"id":519182,"name":"Andrew Cox","orcid":"0000-0003-3485-8892","position":6,"is_corresponding":false},{"id":1489,"name":"Adolfo Garcı́a-Sastre","orcid":"0000-0002-6551-1827","position":7,"is_corresponding":false},{"id":103720,"name":"Randy A. Albrecht","orcid":"0000-0003-4008-503X","position":8,"is_corresponding":false},{"id":519184,"name":"Stephen Dewhurst","orcid":"0000-0001-7729-7920","position":9,"is_corresponding":false},{"id":2423,"name":"Luis Martínez‐Sobrido","orcid":"0000-0001-7084-0804","position":10,"is_corresponding":false},{"id":364881,"name":"Aitor Nogales","orcid":"0000-0002-2424-7900","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-19T00:29:15.734856Z","pmid":"35583364","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":[]}