{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T23:43:58Z","timestamp":1789688638656,"version":"4.0.1"},"posted":{"date-parts":[[2026,2,23]]},"group-title":"Immunology","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R01AI165821"],"award-info":[{"award-number":["R01AI165821"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["U01AI153700"],"award-info":[{"award-number":["U01AI153700"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["75N93021C00015"],"award-info":[{"award-number":["75N93021C00015"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,20]]},"abstract":"<jats:p>The 2023\/2024 influenza vaccine included an updated H1N1 component designed to better match a new clade of H1N1 that had multiple mutations in antigenic epitopes of hemagglutinin. Despite this update, the vaccine trended towards being less effective against the vaccine-matched H1N1 clade than the parental H1N1 clade lacking the new antigenic mutations. Here we measure neutralization titers of serum antibodies from individuals who had received either a recombinant protein or an egg-derived vaccine against a set of viruses with hemagglutinins from 58 H1N1 strains representative of the diversity during the 2023\/2024 season. We find that egg-derived vaccine recipients, but not recombinant protein vaccine recipients, had a relatively lower boost in neutralizing titers to the new clade that the updated vaccine was designed to target. We suggest that the difference in the extent that the egg-derived versus recombinant protein vaccines boost neutralizing titers to the new H1N1 clade is because the seed strain for the egg-derived vaccine strain had acquired a reversion of a key antigenic mutation (K142R) present in that clade. Our results show how egg-derived versus recombinant protein vaccines can elicit different relative titer boosts against different subsets of viral strains, a phenomenon that could impact vaccine effectiveness.<\/jats:p>","DOI":"10.64898\/2026.02.23.707528","type":"posted-content","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T03:20:22Z","timestamp":1771903222000},"source":"Crossref","is-referenced-by-count":1,"title":["Strain-specific differences in the response to egg-derived versus recombinant protein influenza vaccines"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8659-0149","authenticated-orcid":false,"given":"Andrea N","family":"Loes","sequence":"first","affiliation":[{"name":"Fred Hutchinson Cancer Center;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario AL","family":"Tarabi","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuk H","family":"Li","sequence":"additional","affiliation":[{"name":"University of Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reilly K","family":"Atkinson","sequence":"additional","affiliation":[{"name":"University of Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4250-2063","authenticated-orcid":false,"given":"John","family":"Huddleston","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8654-5663","authenticated-orcid":false,"given":"Caroline","family":"Kikawa","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tachianna","family":"Griffths","sequence":"additional","affiliation":[{"name":"University of Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M","family":"Drapeau","sequence":"additional","affiliation":[{"name":"University of Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sook-San","family":"Wong","sequence":"additional","affiliation":[{"name":"University of Hong Kong;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel MS","family":"Cheng","sequence":"additional","affiliation":[{"name":"University of Hong Kong;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7314-840X","authenticated-orcid":false,"given":"Nancy HL","family":"Leung","sequence":"additional","affiliation":[{"name":"University of Hong Kong;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5298-8979","authenticated-orcid":false,"given":"Sarah","family":"Cobey","sequence":"additional","affiliation":[{"name":"University of Chicago;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6297-7154","authenticated-orcid":false,"given":"Benjamin J","family":"Cowling","sequence":"additional","affiliation":[{"name":"University of Hong Kong;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4039-5794","authenticated-orcid":false,"given":"Trevor","family":"Bedford","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott E","family":"Hensley","sequence":"additional","affiliation":[{"name":"University of Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1267-3408","authenticated-orcid":false,"given":"Jesse D","family":"Bloom","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.02.23.707528","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T03:20:11Z","timestamp":1776741611000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.02.23.707528"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,23]]},"references-count":0,"URL":"https:\/\/doi.org\/10.64898\/2026.02.23.707528","relation":{},"subject":[],"published":{"date-parts":[[2026,2,23]]},"subtype":"preprint"}}