Lorin Adams, Phoebe Stevenson-Leggett, Jia Le Lee, James Bazire, Giulia Dowgier, Agnieszka Hobbs, Chloë Roustan, Annabel Borg, Christine Carr, Silvia Innocentin, Louise M. C. Webb, Callie Smith, Philip Bawumia, Nicola Lewis, Nicola O'Reilly, Svend Kjaer, Michelle A. Linterman, Ruth Harvey, Mary Y. Wu, Edward J. Carr
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Here, we adapt our high-throughput live virus microneutralisation (LV-N) assay for SARS-CoV-2, benchmark against HAI assays, and report serological vaccine responsiveness in a cohort of older (> 65 yo) community dwelling adults.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Influenza-specific antibody responses were assessed in 73 individuals, before and after receipt of the adjuvanted 2021–22 Northern Hemisphere quadrivalent vaccine. We performed both HAI and LV-N assays against all four viruses represented in the vaccine [A/Cambodia/e0826360/2020 (H3N2), IVR-215 (A/Victoria/2570/2019-like) (H1N1)pdm09, B/Phuket/3073/2013 (B/Yamagata lineage), B/Washington/02/2019 (B/Victoria lineage)], using sera drawn before vaccination [range: d-82 to d-5], and days 7 [d6–10] and 181 [d156–200] after vaccination. We compared serological responses within each assay and between assays.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Both the traditional HAI assay and our high-throughput live virus microneutralisation identified vaccine-induced boosts in antibody titres. We found population-level concordance between the two assays (Spearman's correlation coefficient range 0.49–0.88; all <i>p</i> ≤ 1.4 × 10<sup>−5</sup>). The improved granularity of microneutralisation was better able to estimate fold changes of responses and quantify the inhibitory effect of pre-existing antibody.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Our high-throughput method offers an alternative approach to assess influenza-specific 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-change in systems vaccinology, and a facet of laboratory-based pandemic preparedness.</p>\n </section>\n </div>","PeriodicalId":13544,"journal":{"name":"Influenza and Other Respiratory Viruses","volume":"19 8","pages":""},"PeriodicalIF":4.2000,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/irv.70140","citationCount":"0","resultStr":"{\"title\":\"Improved Resolution of Influenza Vaccination Responses With High-Throughput Live Virus Microneutralisation\",\"authors\":\"Lorin Adams, Phoebe Stevenson-Leggett, Jia Le Lee, James Bazire, Giulia Dowgier, Agnieszka Hobbs, Chloë Roustan, Annabel Borg, Christine Carr, Silvia Innocentin, Louise M. 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Here, we adapt our high-throughput live virus microneutralisation (LV-N) assay for SARS-CoV-2, benchmark against HAI assays, and report serological vaccine responsiveness in a cohort of older (> 65 yo) community dwelling adults.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Influenza-specific antibody responses were assessed in 73 individuals, before and after receipt of the adjuvanted 2021–22 Northern Hemisphere quadrivalent vaccine. We performed both HAI and LV-N assays against all four viruses represented in the vaccine [A/Cambodia/e0826360/2020 (H3N2), IVR-215 (A/Victoria/2570/2019-like) (H1N1)pdm09, B/Phuket/3073/2013 (B/Yamagata lineage), B/Washington/02/2019 (B/Victoria lineage)], using sera drawn before vaccination [range: d-82 to d-5], and days 7 [d6–10] and 181 [d156–200] after vaccination. We compared serological responses within each assay and between assays.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Both the traditional HAI assay and our high-throughput live virus microneutralisation identified vaccine-induced boosts in antibody titres. We found population-level concordance between the two assays (Spearman's correlation coefficient range 0.49–0.88; all <i>p</i> ≤ 1.4 × 10<sup>−5</sup>). The improved granularity of microneutralisation was better able to estimate fold changes of responses and quantify the inhibitory effect of pre-existing antibody.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>Our high-throughput method offers an alternative approach to assess influenza-specific 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-change in systems vaccinology, and a facet of laboratory-based pandemic preparedness.</p>\\n </section>\\n </div>\",\"PeriodicalId\":13544,\"journal\":{\"name\":\"Influenza and Other Respiratory Viruses\",\"volume\":\"19 8\",\"pages\":\"\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2025-08-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/irv.70140\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Influenza and Other Respiratory Viruses\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/irv.70140\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Influenza and Other Respiratory Viruses","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/irv.70140","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
Improved Resolution of Influenza Vaccination Responses With High-Throughput Live Virus Microneutralisation
Background
Influenza remains a significant threat to human and animal health. 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-throughput live virus microneutralisation (LV-N) assay for SARS-CoV-2, benchmark against HAI assays, and report serological vaccine responsiveness in a cohort of older (> 65 yo) community dwelling adults.
Methods
Influenza-specific antibody responses were assessed in 73 individuals, before and after receipt of the adjuvanted 2021–22 Northern Hemisphere quadrivalent vaccine. We performed both HAI and LV-N assays against all four viruses represented in the vaccine [A/Cambodia/e0826360/2020 (H3N2), IVR-215 (A/Victoria/2570/2019-like) (H1N1)pdm09, B/Phuket/3073/2013 (B/Yamagata lineage), B/Washington/02/2019 (B/Victoria lineage)], using sera drawn before vaccination [range: d-82 to d-5], and days 7 [d6–10] and 181 [d156–200] after vaccination. We compared serological responses within each assay and between assays.
Results
Both the traditional HAI assay and our high-throughput live virus microneutralisation identified vaccine-induced boosts in antibody titres. We found population-level concordance between the two assays (Spearman's correlation coefficient range 0.49–0.88; all p ≤ 1.4 × 10−5). The improved granularity of microneutralisation was better able to estimate fold changes of responses and quantify the inhibitory effect of pre-existing antibody.
Conclusions
Our high-throughput method offers an alternative approach to assess influenza-specific 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-change in systems vaccinology, and a facet of laboratory-based pandemic preparedness.
期刊介绍：
Influenza and Other Respiratory Viruses is the official journal of the International Society of Influenza and Other Respiratory Virus Diseases - an independent scientific professional society - dedicated to promoting the prevention, detection, treatment, and control of influenza and other respiratory virus diseases.
Influenza and Other Respiratory Viruses is an Open Access journal. Copyright on any research article published by Influenza and Other Respiratory Viruses is retained by the author(s). Authors grant Wiley a license to publish the article and identify itself as the original publisher. Authors also grant any third party the right to use the article freely as long as its integrity is maintained and its original authors, citation details and publisher are identified.
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