{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:55:09Z","timestamp":1790402109602,"version":"4.1.0"},"reference-count":59,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"13","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2023,3,31]]},"abstract":"<jats:p>During influenza virus entry, the hemagglutinin (HA) protein binds receptors and causes membrane fusion after endosomal acid activation. To improve vaccine efficiency and pandemic risk assessment for currently-dominant H3N2 influenza viruses, we investigated HA stability of 6 vaccine reference viruses and 42 circulating viruses. Recent vaccine reference viruses had destabilized HA proteins due to egg-adaptive mutation HA1-L194P. Virus growth in cell culture was independent of HA stability. In ferrets, the vaccine reference viruses and circulating viruses required a relatively stable HA (activation and inactivation pH\u00a0&lt;\u00a05.5) for airborne transmissibility. The recent vaccine reference viruses with destabilized HA proteins had reduced infectivity, had no airborne transmissibility unless reversion to HA1-P194L occurred, and had skewed antigenicity away from the studied viruses and circulating H3N2 viruses. Other vaccine reference viruses with stabilized HAs retained infectivity, transmissibility, and antigenicity. Therefore, HA stabilization should be prioritized over destabilization in vaccine reference virus selection to reduce mismatches between vaccine and circulating viruses.<\/jats:p>","DOI":"10.1126\/sciadv.adf5182","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T14:02:09Z","timestamp":1681135329000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":15,"title":["Hemagglutinin destabilization in H3N2 vaccine reference viruses skews antigenicity and prevents airborne transmission in ferrets"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9550-0926","authenticated-orcid":true,"given":"Meng","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, St.\u00a0Jude Children\u2019s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5329-4175","authenticated-orcid":true,"given":"Christina","family":"Kackos","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St.\u00a0Jude Children\u2019s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA."},{"name":"St.\u00a0Jude Children\u2019s Research Hospital Graduate School of Biomedical Sciences, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balaji","family":"Banoth","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St.\u00a0Jude Children\u2019s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6816-8892","authenticated-orcid":true,"given":"Chet Raj","family":"Ojha","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St.\u00a0Jude Children\u2019s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9980-2112","authenticated-orcid":true,"given":"Jeremy C.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St.\u00a0Jude Children\u2019s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohua","family":"Lei","sequence":"additional","affiliation":[{"name":"Center for Applied Bioinformatics, St.\u00a0Jude Children\u2019s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA."},{"name":"Center of Excellence for Leukemia Studies, St.\u00a0Jude Children\u2019s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8828-5199","authenticated-orcid":true,"given":"Lei","family":"Li","sequence":"additional","affiliation":[{"name":"Drukier Institute for Children\u2019s Health, Department of Pediatrics, Weill Cornell Medicine, New\u00a0York, NY 10021, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6300-0452","authenticated-orcid":true,"given":"Lisa","family":"Kercher","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St.\u00a0Jude Children\u2019s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4397-7132","authenticated-orcid":true,"given":"Richard J.","family":"Webby","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St.\u00a0Jude Children\u2019s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA."},{"name":"Department of Microbiology, Immunology and Biochemistry, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5683-3990","authenticated-orcid":true,"given":"Charles J.","family":"Russell","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St.\u00a0Jude Children\u2019s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA."},{"name":"Department of Microbiology, Immunology and Biochemistry, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/emi.2014.9"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2018.03.005"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0115-z"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29402-5"},{"key":"e_1_3_3_6_2","unstructured":"Centers for Disease Control and Prevention Weekly U.S. Influenza Surveillance Report updated 21 October 2022; www.cdc.gov\/flu\/weekly\/index.htm."},{"key":"e_1_3_3_7_2","unstructured":"World Health Organization Influenza Update 3 October 2022; www.who.int\/publications\/m\/item\/influenza-update-n-429."},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2018.1462639"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01763-16"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1119945109"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01009-20"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2309.170847"},{"key":"e_1_3_3_13_2","unstructured":"Centers for Disease Control and Prevention Influenza Risk Assessment Tool (IRAT) reviewed 27 November 2020; www.cdc.gov\/flu\/pandemic-resources\/national-strategy\/risk-assessment.htm."},{"key":"e_1_3_3_14_2","unstructured":"World Health Organization Tool for Influenza Pandemic Risk Assessment (TIPRA) May 2016; https:\/\/apps.who.int\/iris\/handle\/10665\/250130."},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz8822"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.69.1.531"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003151"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.56236"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009910"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00665-18"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006276"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00100-22"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0264-410X(85)90109-4"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.3390\/v13050719"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008362"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00058-19"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00246-17"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01423-19"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01174-22"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abm5859"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.06.043"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32926-5"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1213362"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10831"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.02.040"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1524384113"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29950-w"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a038315"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw635"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1097211"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25713-1"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2005.03.010"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1712377114"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.000457"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006682"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2019.04.013"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010875"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2018.1460297"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2010.03.078"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.02.100"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00058-10"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0042-6822(03)00377-5"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2021.04.057"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.11.6763-6771.2005"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003831"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.4161\/hv.29340"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep37800"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2016.11.008"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01175-13"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02737-09"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adf5182","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T21:20:21Z","timestamp":1704835221000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adf5182"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,31]]},"references-count":59,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2023,3,31]]}},"alternative-id":["10.1126\/sciadv.adf5182"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adf5182","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,31]]},"assertion":[{"value":"2022-10-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadf5182"}}