Licensed influenza virus vaccines target the head domain of the hemagglutinin (HA) glycoprotein which undergoes constant antigenic drift. The highly conserved HA stalk domain is an attractive target to increase immunologic breadth required for universal influenza virus vaccines. We tested the hypothesis that immunization with a pandemic influenza virus vaccine boosts pre-existing anti-stalk antibodies. We used chimeric cH6/1, full length H2 and H18 HA antigens in an ELISA to measure anti-stalk antibodies in recipients participating in clinical trials of A/H1N1, A/H5N1 and A/H9N2 vaccines. The vaccines induced high titers of anti-H1 stalk antibodies in adults and children, with higher titers elicited by AS03-adjuvanted vaccines. We also observed cross-reactivity to H2 and H18 HAs. The A/H9N2 vaccine elicited plasmablast and memory B-cell responses. Post-vaccination serum from vaccinees protected mice against lethal challenge with cH6/1N5 and cH5/3N4 viruses. These findings support the concept of a chimeric HA stalk-based universal influenza virus vaccine. clinicaltrials.gov: NCT02415842.

中文翻译：

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大流行性流感病毒疫苗可增强初次成年和小儿队列中的血凝素茎特异性抗体反应。

许可的流感病毒疫苗的目标是血凝素（HA）糖蛋白的头部结构域，该结构域会不断发生抗原性漂移。高度保守的HA茎结构域是增加通用流感病毒疫苗所需的免疫广度的有吸引力的目标。我们检验了使用大流行性流感病毒疫苗进行免疫可增强现有抗茎杆抗体的假说。我们在ELISA中使用了嵌合的cH6 / 1，全长H2和H18 HA抗原来测量参加A / H1N1，A / H5N1和A / H9N2疫苗临床试验的受试者的抗茎抗体。该疫苗在成人和儿童中诱导出高滴度的抗H1茎抗体，而AS03辅助疫苗则引起较高的滴度。我们还观察到与H2和H18 HA的交叉反应性。A / H9N2疫苗引起浆母细胞和记忆B细胞反应。疫苗接种后的血清可保护小鼠免受cH6 / 1N5和cH5 / 3N4病毒的致命攻击。这些发现支持了基于嵌合HA杆的通用流感病毒疫苗的概念。Clinicaltrials.gov：NCT02415842。