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Assessing serological protection against influenza has relied upon haemagglutinin inhibition (HAI) assays, which are used to gauge existing immune landscapes, seasonal vaccine decisions and in systems vaccinology studies. HAI assays were first described in the 1940s. Here, we adapt our high\u2010throughput live virus microneutralisation (LV\u2010N) assay for SARS\u2010CoV\u20102, benchmark against HAI assays, and report serological vaccine responsiveness in a cohort of older (&gt;\u200965\u2009yo) community dwelling adults.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Influenza\u2010specific antibody responses were assessed in 73 individuals, before and after receipt of the adjuvanted 2021\u201322 Northern Hemisphere quadrivalent vaccine. We performed both HAI and LV\u2010N assays against all four viruses represented in the vaccine [A\/Cambodia\/e0826360\/2020 (H3N2), IVR\u2010215 (A\/Victoria\/2570\/2019\u2010like) (H1N1)pdm09, B\/Phuket\/3073\/2013 (B\/Yamagata lineage), B\/Washington\/02\/2019 (B\/Victoria lineage)], using sera drawn before vaccination [range: d\u201082 to d\u20105], and days 7 [d6\u201310] and 181 [d156\u2013200] after vaccination. We compared serological responses within each assay and between assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both the traditional HAI assay and our high\u2010throughput live virus microneutralisation identified vaccine\u2010induced boosts in antibody titres. We found population\u2010level concordance between the two assays (Spearman's correlation coefficient range 0.49\u20130.88; all <jats:italic>p<\/jats:italic>\u2009\u2264\u20091.4\u2009\u00d7\u200910<jats:sup>\u22125<\/jats:sup>). The improved granularity of microneutralisation was better able to estimate fold changes of responses and quantify the inhibitory effect of pre\u2010existing antibody.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our high\u2010throughput method offers an alternative approach to assess influenza\u2010specific serological responses with improved resolution, with the potential to improve the annual assessment of existing antibody landscapes, to improve new vaccine strain evaluation, and to offer a step\u2010change in systems vaccinology, and a facet of laboratory\u2010based pandemic preparedness.<\/jats:p><\/jats:sec>","DOI":"10.1111\/irv.70140","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:05:08Z","timestamp":1755216308000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Improved Resolution of Influenza Vaccination Responses With High\u2010Throughput Live Virus Microneutralisation"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8357-2327","authenticated-orcid":false,"given":"Lorin","family":"Adams","sequence":"first","affiliation":[{"name":"Worldwide Influenza Centre The Francis Crick Institute  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6509-3354","authenticated-orcid":false,"given":"Phoebe","family":"Stevenson\u2010Leggett","sequence":"additional","affiliation":[{"name":"COVID Surveillance Unit The Francis Crick Institute  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1600-6437","authenticated-orcid":false,"given":"Jia\u00a0Le","family":"Lee","sequence":"additional","affiliation":[{"name":"Immunology Program Babraham Institute  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7094-5021","authenticated-orcid":false,"given":"James","family":"Bazire","sequence":"additional","affiliation":[{"name":"COVID Surveillance Unit The Francis Crick Institute  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6738-5097","authenticated-orcid":false,"given":"Giulia","family":"Dowgier","sequence":"additional","affiliation":[{"name":"COVID Surveillance Unit The Francis Crick Institute  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Hobbs","sequence":"additional","affiliation":[{"name":"COVID Surveillance Unit The Francis Crick Institute  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chlo\u00eb","family":"Roustan","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute  London 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