{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:47:27Z","timestamp":1789753647244,"version":"4.0.1"},"reference-count":79,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"37","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2023,9,15]]},"abstract":"<jats:p>Seasonal influenza virus vaccines are effective when they are well matched to circulating strains. Because of antigenic drift\/change in the immunodominant hemagglutinin (HA) head domain, annual vaccine reformulations are necessary to maintain a match with circulating strains. In addition, seasonal vaccines provide little to no protection against newly emerging pandemic strains. Sequential vaccination with chimeric HA (cHA) constructs has been proven to direct the immune response toward the immunosubdominant but more conserved HA stalk domain. In this study, we show that immunization with group 2 cHA split vaccines in combination with the CpG 1018 adjuvant elicits broadly cross-reactive antibodies against all group 2 HAs, as well as systemic and local antigen-specific T cell responses. Antibodies elicited after sequential vaccination are directed to conserved regions of the HA such as the stalk and the trimer interface and also to the N2 neuraminidase (NA). Immunized mice were fully protected from challenge with a broad panel of influenza A viruses.<\/jats:p>","DOI":"10.1126\/sciadv.adi4753","type":"journal-article","created":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T13:58:50Z","timestamp":1694613530000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":41,"title":["Chimeric hemagglutinin split vaccines elicit broadly cross-reactive antibodies and protection against group 2 influenza viruses in mice"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2816-7051","authenticated-orcid":true,"given":"Eduard","family":"Puente-Massaguer","sequence":"first","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New\u00a0York, NY 10029, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7750-9652","authenticated-orcid":true,"given":"Kirill","family":"Vasilev","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New\u00a0York, NY 10029, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2741-9904","authenticated-orcid":true,"given":"Annika","family":"Beyer","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New\u00a0York, NY 10029, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3751-8036","authenticated-orcid":true,"given":"Madhumathi","family":"Loganathan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New\u00a0York, NY 10029, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5176-6535","authenticated-orcid":true,"given":"Benjamin","family":"Francis","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New\u00a0York, NY 10029, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3289-9159","authenticated-orcid":true,"given":"Michael J.","family":"Scherm","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New\u00a0York, NY 10029, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3665-2708","authenticated-orcid":true,"given":"Guha Asthagiri","family":"Arunkumar","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New\u00a0York, NY 10029, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7920-5505","authenticated-orcid":true,"given":"Irene","family":"Gonz\u00e1lez-Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New\u00a0York, NY 10029, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6021-3740","authenticated-orcid":true,"given":"Xueyong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6469-2419","authenticated-orcid":true,"given":"Ian A.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA."},{"name":"Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9880-6560","authenticated-orcid":true,"given":"Lynda","family":"Coughlan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA."},{"name":"Center for Vaccine Development and Global Health (CVD), University of Maryland School of Medicine, Baltimore, MD 21201, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2435-5047","authenticated-orcid":true,"given":"Weina","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New\u00a0York, NY 10029, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0337-5823","authenticated-orcid":true,"given":"Peter","family":"Palese","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New\u00a0York, NY 10029, USA."},{"name":"Department of Medicine, Icahn School of Medicine at Mount Sinai, New\u00a0York, NY 10029, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4121-776X","authenticated-orcid":true,"given":"Florian","family":"Krammer","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New\u00a0York, NY 10029, USA."},{"name":"Department of Pathology, Icahn School of Medicine at Mount Sinai, New\u00a0York, NY 10029, USA."},{"name":"Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New\u00a0York, NY 10029, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz411"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2021.01.032"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1525578113"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1266\/ggs.86.287"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2020.06.021"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz865"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(22)00192-6"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2308.170600"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60111-2"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.21037\/qims-21-592"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a038448"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a028845"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111628"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00286-17"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02608-13"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.10.015"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2206333119"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3927"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.04.018"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00137-12"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03060-15"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2200821119"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/npjvaccines.2016.15"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines9010040"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-017-0026-4"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-1118-7"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00024-X"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30393-7"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03183-13"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01715-13"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-6445-1_2"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01996-15"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3684"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aag1322"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a038471"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01526-18"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00228-07"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines6030047"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02005"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2023.1097349"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1080\/14760584.2021.1908133"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1205669"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3443"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01696-18"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.04.011"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv195"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02556-14"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2017.1377376"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2018.03.013"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2019.04.055"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-77077-z"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00241-5"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37162-z"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00641-13"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2274"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2006.00395.x"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.746447"},{"key":"e_1_3_2_59_2","first-page":"e51112","article-title":"Expression of functional recombinant hemagglutinin and neuraminidase proteins from the novel H7N9 influenza virus using the baculovirus expression system","author":"Margine I.","year":"2013","unstructured":"I.\u00a0Margine, P.\u00a0Palese, F.\u00a0Krammer, Expression of functional recombinant hemagglutinin and neuraminidase proteins from the novel H7N9 influenza virus using the baculovirus expression system. J. Vis. Exp., e51112 (2013).","journal-title":"J. Vis. Exp."},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2022.01.011"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0194830"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00819-13"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00609-11"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-019-0126-4"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02281-16"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00958-20"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01076-08"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2019.1637284"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2018.1564369"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41426-018-0115-0"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3854"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2015.01.026"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01213-08"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000796"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.465"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02090-20"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05930-11"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2020.11.057"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty407"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2011.75"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adi4753","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T17:19:41Z","timestamp":1704820781000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adi4753"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,15]]},"references-count":79,"journal-issue":{"issue":"37","published-print":{"date-parts":[[2023,9,15]]}},"alternative-id":["10.1126\/sciadv.adi4753"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adi4753","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,15]]},"assertion":[{"value":"2023-04-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadi4753"}}