抗神经氨酸酶和抗血凝素柄对不同甲型H7N9流感疫苗方案的反应

IF 4.5 3区 医学 Q2 IMMUNOLOGY Vaccine Pub Date : 2025-02-15 Epub Date: 2025-01-04 DOI:10.1016/j.vaccine.2024.126689
Hana M. El Sahly , Evan J. Anderson , Lisa A. Jackson , Kathleen M. Neuzil , Robert L. Atmar , David I. Bernstein , Wilbur H. Chen , C. Buddy Creech , Sharon E. Frey , Paul Goepfert , Jeffery Meier , Varun Phadke , Nadine Rouphael , Richard Rupp , Jack T. Stapleton , Paul Spearman , Emmanuel B. Walter , Patricia L. Winokur , Inci Yildirim , Tracie L. Williams , Paul C. Roberts
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引用次数: 0

摘要

大流行性流感疫苗的开发重点是血凝素(HA)抗原的效力和免疫原性。针对神经氨酸酶(NA)抗原或HA柄结构域的抗体反应与流感的保护有关。人类在大流行灭活流感后对NA和HA-stalk结构域的反应尚未得到很好的表征。材料和方法:在一系列临床试验中,我们确定了疫苗的NA含量,并证明在用as03佐剂的a (H7N9) IIV灭活疫苗(a (H7N9) IIV)启动2次系列后,NA抑制(NAI)抗体应答以剂量依赖的方式增加,NAI抗体应答也随着2次系列启动间隔的延长或用异种佐剂的a (H7N9) IIV延迟5年增强而增加。同时或先后接种季节性流感疫苗,以及在2剂引物系列中使用异源甲型H7N9病毒,均未对NAI抗体反应产生明显影响。抗血凝素茎抗体反应很小且不持久。结论:我们为提高抗神经氨酸酶反应的策略提供了证据,这些策略可以进一步标准化,以备大流行。临床试验注册号:NCT03312231, NCT03318315, NCT03589807, NCT03738241。
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Anti-neuraminidase and anti-hemagglutinin stalk responses to different influenza a(H7N9) vaccine regimens

Introduction

Pandemic influenza vaccine development focuses on the hemagglutinin (HA) antigen for potency and immunogenicity. Antibody responses targeting the neuraminidase (NA) antigen, or the HA stalk domain have been implicated in protection against influenza. Responses to the NA and HA-stalk domain following pandemic inactivated influenza are not well characterized in humans.

Material and methods

In a series of clinical trials, we determine the vaccines' NA content and demonstrate that NA inhibition (NAI) antibody responses increase in a dose-dependent manner following a 2-dose priming series with AS03-adjuvanted influenza A(H7N9) inactivated vaccine (A(H7N9) IIV). NAI antibody responses also increase with interval extension of the 2-dose priming series or following a 5-year delayed boost with a heterologous adjuvanted A(H7N9) IIV. Neither concomitant seasonal influenza vaccination given simultaneously or sequentially, nor use of heterologous A(H7N9) IIVs in the 2-dose priming series had an appreciable effect on NAI antibody responses. Anti-HA stalk antibody responses were minimal and not durable.

Conclusions

We provide evidence for strategies to improve anti-neuraminidase responses which can be further standardized for pandemic preparedness.

Clinical Trial Registry Numbers

NCT03312231, NCT03318315, NCT03589807, NCT03738241.
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来源期刊
Vaccine
Vaccine 医学-免疫学
CiteScore
8.70
自引率
5.50%
发文量
992
审稿时长
131 days
期刊介绍: Vaccine is unique in publishing the highest quality science across all disciplines relevant to the field of vaccinology - all original article submissions across basic and clinical research, vaccine manufacturing, history, public policy, behavioral science and ethics, social sciences, safety, and many other related areas are welcomed. The submission categories as given in the Guide for Authors indicate where we receive the most papers. Papers outside these major areas are also welcome and authors are encouraged to contact us with specific questions.
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