针对不同甲型H7N9流感疫苗接种方案的抗神经氨酸酶和抗血凝素茎反应。
Anti-neuraminidase and anti-hemagglutinin stalk responses to different influenza a(H7N9) vaccine regimens.
作者信息
El Sahly Hana M, Anderson Evan J, Jackson Lisa A, Neuzil Kathleen M, Atmar Robert L, Bernstein David I, Chen Wilbur H, Creech C Buddy, Frey Sharon E, Goepfert Paul, Meier Jeffery, Phadke Varun, Rouphael Nadine, Rupp Richard, Stapleton Jack T, Spearman Paul, Walter Emmanuel B, Winokur Patricia L, Yildirim Inci, Williams Tracie L, Oshinsky Jennifer, Coughlan Lynda, Nijhuis Haye, Pasetti Marcela F, Krammer Florian, Stadlbauer Daniel, Nachbagauer Raffael, Tsong Rachel, Wegel Ashley, Roberts Paul C
机构信息
Departments of Molecular Virology and Microbiology and Medicine, Baylor College of Medicine, Houston, TX, United States.
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, United States.
出版信息
Vaccine. 2025 Feb 15;47:126689. doi: 10.1016/j.vaccine.2024.126689. Epub 2025 Jan 4.
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.
引言
大流行性流感疫苗的研发主要聚焦于血凝素（HA）抗原的效力和免疫原性。针对神经氨酸酶（NA）抗原或HA茎区的抗体反应与流感防护有关。在人类中，大流行性灭活流感疫苗接种后对NA和HA茎区的反应尚未得到充分表征。
材料与方法
在一系列临床试验中，我们测定了疫苗的NA含量，并证明在使用AS03佐剂的甲型H7N9流感灭活疫苗（A(H7N9) IIV）进行两剂初免后，NA抑制（NAI）抗体反应呈剂量依赖性增加。NAI抗体反应也会随着两剂初免系列间隔时间的延长或在5年后用异源佐剂A(H7N9) IIV进行延迟加强接种而增加。同时或先后接种季节性流感疫苗，以及在两剂初免系列中使用异源A(H7N9) IIV，均对NAI抗体反应没有明显影响。抗HA茎区抗体反应微弱且不持久。
结论
我们为改善抗神经氨酸酶反应的策略提供了证据，这些策略可进一步标准化以应对大流行。
临床试验注册号
NCT03312231、NCT03318315、NCT03589807、NCT03738241。
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