{"doi":"10.1101/2022.07.06.499081","title":"Nucleoside-modified mRNA-based influenza vaccines circumvent problems associated with H3N2 vaccine strain egg-adaptation","abstract":"ABSTRACT Most human influenza vaccine antigens are produced in fertilized chicken eggs. Recent H3N2 egg-based vaccine antigens have limited effectiveness, partially due to egg-adaptive substitutions that alter the antigenicity of the hemagglutinin (HA) protein. The nucleoside-modified messenger RNA encapsulated in lipid nanoparticle (mRNA-LNP) vaccine platform is a promising alternative for egg-based influenza vaccines because mRNA-LNP-derived antigens are not subject to adaptive pressures that arise during the production of antigens in chicken eggs. Here, we compared H3N2-specific antibody responses in mice vaccinated with either 3c.2A H3-encoded mRNA-LNP or a conventional egg-based Fluzone vaccine (which included an egg-adapted 3c.2A antigen) supplemented with an MF59-like adjuvant. We tested mRNA-LNP encoding wild-type and egg-adapted 3c.2A H3 antigens. We found that mRNA-LNP encoding wild-type 3c.2A H3 elicited antibodies that neutralized the wild-type 3c.2A H3N2 virus more effectively relative to antibodies elicited by mRNA-LNP encoding egg-adapted 3c2.A H3 or the egg-based Fluzone vaccine. mRNA-LNP expressing either wild-type or egg-adapted 3c2.A H3 protected mice against infection with the wild-type 3c2.A H3N2, whereas the egg-based Fluzone vaccine did not. We found that both mRNA-LNP vaccines elicited high levels of group 2 HA stalk-reactive antibodies that likely contributed to protection in vivo . Our studies indicate that nucleoside-modified mRNA-LNP-based vaccines can circumvent problems associated with egg-adaptations with recent 3c2.A H3N2 viruses. Summary This study shows that the nucleoside-modified messenger RNA encapsulated in lipid nanoparticle (mRNA-LNP) vaccine platform is a promising alternative for egg-based influenza vaccines. We show that mRNA-LNP expressing H3 antigens elicit high levels of antibodies in mice and protect against H3N2 influenza virus infection.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":301511,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9519,"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":322933,"name":"Kaela Parkhouse","orcid":"0000-0001-7608-4464","position":1,"is_corresponding":false},{"id":105468,"name":"Madison E. Weirick","orcid":"0000-0003-2112-8102","position":2,"is_corresponding":false},{"id":20749,"name":"Hiromi Muramatsu","orcid":"0000-0003-1544-1493","position":3,"is_corresponding":false},{"id":54904,"name":"Norbert Pardi","orcid":"0000-0003-1008-6242","position":4,"is_corresponding":false},{"id":233975,"name":"Steven H.Y. Fan","orcid":null,"position":5,"is_corresponding":false},{"id":20753,"name":"Drew Weissman","orcid":"0000-0002-1501-6510","position":6,"is_corresponding":false},{"id":105476,"name":"Scott E. Hensley","orcid":"0000-0002-2928-7506","position":7,"is_corresponding":false},{"id":105469,"name":"Sigrid Gouma","orcid":"0000-0002-7853-8340","position":0,"is_corresponding":true}],"reference_count":15,"raw_metadata":null,"created_at":"2026-07-19T00:32:02.193874Z","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":[]}