Improved Resolution of Influenza Vaccination Responses With High-Throughput Live Virus Microneutralisation

IF 4.2 4区医学 Q1 INFECTIOUS DISEASES

Influenza and Other Respiratory Viruses Pub Date : 2025-08-14 DOI:10.1111/irv.70140

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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引用次数: 0

Abstract

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.

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用高通量活病毒微量中和技术提高流感疫苗应答的分辨率

流感仍然是对人类和动物健康的重大威胁。评估对流感的血清学保护依赖于血凝素抑制（HAI）测定，这种测定用于衡量现有的免疫格局、季节性疫苗决策和系统疫苗学研究。HAI测定法在20世纪40年代首次被描述。在这里，我们将我们的高通量活病毒微量中和（LV-N）试验用于SARS-CoV-2，作为与HAI试验的基准，并报告了一组老年（65岁）社区居住成年人的血清学疫苗反应性。方法对73例接种2021-22北半球四价佐剂疫苗前后的流感特异性抗体反应进行了评估。我们对疫苗中代表的所有四种病毒[A/Cambodia/e0826360/2020 (H3N2), IVR-215 (A/Victoria/2570/2019-like) (H1N1)pdm09, B/Phuket/3073/2013 （B/Yamagata谱系），B/Washington/02/2019 （B/Victoria谱系）]进行了HAI和lc - n检测，使用接种前[范围：d-82至d-5]和接种后第7天[d6-10]和第181天[d156-200]抽取的血清。我们比较了每次检测内和检测间的血清学反应。结果传统的HAI试验和我们的高通量活病毒微量中和试验均鉴定出疫苗诱导的抗体滴度增强。我们发现两种检测方法在人群水平上是一致的(Spearman相关系数范围为0.49-0.88；均p≤1.4 × 10−5)。改进的微中和粒度能够更好地估计反应的折叠变化，并量化预先存在的抗体的抑制效果。我们的高通量方法提供了一种评估流感特异性血清学反应的替代方法，具有更高的分辨率，有可能改善现有抗体图谱的年度评估，改进新疫苗株评估，并提供系统疫苗学的逐步改变，以及基于实验室的大流行防范的一个方面。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Influenza and Other Respiratory Viruses 医学-病毒学

CiteScore

7.20

自引率

4.50%

发文量

120

审稿时长

6-12 weeks

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.