Avian H5 influenza is an emerging influenza strain with the potential for human pandemic spread. One unresolved issue in pandemic vaccine preparedness is to what extent a vaccine recall response depends on the interval between the priming and boosting vaccinations. In this study, we analyzed the anti-H5 HA IgG responses to an H5 A/Indonesia/5/2005 boosting vaccination in three cohorts: (1) a short interval boosting cohort that received a prime and boost 28 days apart, (2) a long-interval boosting cohort that received an H5 A/Vietnam/203/2004 priming vaccination 5 years before boosting, and (3) a double long-boost cohort that received single doses of all three vaccines separated by 5-6 year intervals. Anti-HA IgG levels were measured using a multiple-plex assay against 21 H5 and 16 seasonal strains covering both influenza phylogenetic groups. We used the antigentic distance between the vaccine strain and each HA in the assay panel to define the antibody response landscape. Both single and double long-interval boosting with the H5 variant vaccine elicited a broad antibody response to all H5 subtype strains, and double boosting resulted in sustained, vaccine-specific, anti-HA IgG levels over a six month period. Antibody-mediated immune responses were shaped by prior H5 exposure history, and the magnitude of both vaccine specific and cross-reactive anti-H5 HA IgG responses was highly correlated with the relative antigenic distance between the measured and the vaccine HAs. We conclude that the relative antibody landscape method can be used to quantify the phenomenon of antigenic imprinting on human influenza vaccine immune responses.

中文翻译：

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交叉反应抗血凝素（HA）IgG反应是由以前的长间隔单价H5疫苗接种形成的，并且与HA抗原距离高度相关

禽H5流感是一种新兴的流感毒株，具有人类大流行传播的潜力。大流行疫苗制备中一个尚未解决的问题是疫苗召回反应在多大程度上取决于初次接种和加强接种之间的间隔。在这项研究中，我们分析了三个队列中针对H5 A /印度尼西亚/ 5/2005增强疫苗接种的抗H5 HA IgG应答：（1）短间隔的增强队列接受了初次免疫，并且间隔28天增强了免疫，（2）一个长间隔的加强免疫队列，在加强免疫前5年接受了H5 A / Vietnam / 203/2004初次接种疫苗；（3）双长期加强免疫队列，接受了所有三种疫苗的单剂，间隔5-6年。使用针对21 H5和16个季节性流感毒株的多重多重测定法测量了抗HA IgG的水平，这些毒株覆盖了两个流感系统发生组。我们使用了检测菌株中疫苗株与每个HA之间的抗原距离来定义抗体反应情况。用H5变体疫苗单次和两次长间隔加强免疫均可引起对所有H5亚型毒株的广泛抗体反应，两次加强免疫可在六个月内持续产生疫苗特异性抗HA IgG水平。抗体介导的免疫反应受以前的H5暴露史影响，疫苗特异性和交叉反应性抗H5 HA IgG免疫反应的强度与所测疫苗与疫苗HA之间的相对抗原距离高度相关。我们得出结论，相对抗体景观方法可以用于量化人类流感疫苗免疫反应上的抗原印迹现象。