Robust immunity to influenza vaccination in haematopoietic stem cell transplant recipients following reconstitution of humoral and adaptive immunity

IF 4.6 2区医学 Q2 IMMUNOLOGY

Clinical & Translational Immunology Pub Date : 2023-06-27 DOI:10.1002/cti2.1456

Wuji Zhang, Louise C Rowntree, Ramona Muttucumaru, Timon Damelang, Malet Aban, Aeron C Hurt, Maria Auladell, Robyn Esterbauer, Bruce Wines, Mark Hogarth, Stephen J Turner, Adam K Wheatley, Stephen J Kent, Sushrut Patil, Sharon Avery, Orla Morrissey, Amy W Chung, Marios Koutsakos, Thi HO Nguyen, Allen C Cheng, Tom C Kotsimbos, Katherine Kedzierska

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引用次数: 1

Abstract

Objectives

Influenza causes significant morbidity and mortality, especially in high-risk populations. Although current vaccination regimens are the best method to combat annual influenza disease, vaccine efficacy can be low in high-risk groups, such as haematopoietic stem cell transplant (HSCT) recipients.

Methods

We comprehensively assessed humoral immunity, antibody landscapes, systems serology and influenza-specific B-cell responses, together with their phenotypes and isotypes, to the inactivated influenza vaccine (IIV) in HSCT recipients in comparison to healthy controls.

Results

Inactivated influenza vaccine significantly increased haemagglutination inhibition (HAI) titres in HSCT recipients, similar to healthy controls. Systems serology revealed increased IgG1 and IgG3 antibody levels towards the haemagglutinin (HA) head, but not to neuraminidase, nucleoprotein or HA stem. IIV also increased frequencies of total, IgG class-switched and CD21^loCD27⁺ influenza-specific B cells, determined by HA probes and flow cytometry. Strikingly, 40% of HSCT recipients had markedly higher antibody responses towards A/H3N2 vaccine strain than healthy controls and showed cross-reactivity to antigenically drifted A/H3N2 strains by antibody landscape analysis. These superior humoral responses were associated with a greater time interval after HSCT, while multivariant analyses revealed the importance of pre-existing immune memory. Conversely, in HSCT recipients who did not respond to the first dose, the second IIV dose did not greatly improve their humoral response, although 50% of second-dose patients reached a seroprotective HAI titre for at least one of vaccine strains.

Conclusions

Our study demonstrates efficient, although time-dependent, immune responses to IIV in HSCT recipients, and provides insights into influenza vaccination strategies targeted to immunocompromised high-risk groups.

Abstract Image

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在体液免疫和适应性免疫重建后，造血干细胞移植受者对流感疫苗接种的强大免疫力

目的流感可导致大量发病率和死亡率，特别是在高危人群中。尽管目前的疫苗接种方案是对抗年度流感疾病的最佳方法，但疫苗效力在高危人群中可能较低，例如造血干细胞移植(HSCT)接受者。方法:与健康对照相比，我们全面评估了造血干细胞移植受者对灭活流感疫苗(IIV)的体液免疫、抗体景观、系统血清学和流感特异性b细胞反应，以及它们的表型和同型。结果灭活流感疫苗显著增加造血干细胞移植受者的血凝抑制(HAI)滴度，与健康对照相似。系统血清学显示针对血凝素(HA)头部的IgG1和IgG3抗体水平升高，但不针对神经氨酸酶、核蛋白或HA茎。通过HA探针和流式细胞术检测，IIV还增加了流感特异性B细胞的总频率、IgG类切换频率和CD21loCD27+频率。引人注目的是，40%的HSCT接受者对A/H3N2疫苗株的抗体反应明显高于健康对照组，并且通过抗体景观分析显示对抗原漂移的A/H3N2株具有交叉反应性。这些优越的体液反应与HSCT后更长的时间间隔有关，而多变量分析揭示了预先存在的免疫记忆的重要性。相反，在对第一次剂量没有反应的HSCT接受者中，第二次IIV剂量并没有大大改善他们的体液反应，尽管50%的第二次剂量患者至少有一种疫苗株达到了血清保护性HAI滴度。我们的研究证明了造血干细胞移植受者对iv的免疫反应是有效的，尽管是时间依赖性的，并为针对免疫功能低下的高危人群的流感疫苗接种策略提供了见解。

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

Clinical & Translational Immunology Medicine-Immunology and Allergy

CiteScore

12.00

自引率

1.70%

发文量

审稿时长

13 weeks

期刊介绍： Clinical & Translational Immunology is an open access, fully peer-reviewed journal devoted to publishing cutting-edge advances in biomedical research for scientists and physicians. The Journal covers fields including cancer biology, cardiovascular research, gene therapy, immunology, vaccine development and disease pathogenesis and therapy at the earliest phases of investigation.