H3N2 Influenza Virus Infection Induces Broadly Reactive Hemagglutinin Stalk Antibodies in Humans and Mice
H3N2 Influenza Virus Infection Induces Broadly Reactive Hemagglutinin Stalk Antibodies in Humans and Mice
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DOI：
10.1128/jvi.03509-12
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发表时间：
2013-04-01
影响因子：
5.4
通讯作者：
Krammer, Florian
中科院分区：
文献类型：
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作者：
Margine, Irina;Hai, Rong;Krammer, Florian
针对病毒血凝素保守茎域的广泛中和抗体近年来引起了越来越多的关注。然而，到目前为止，仅分离到有限数量的针对第2组流感血凝素的茎抗体。此外，对流感病毒疫苗接种或感染诱导这些抗体的一般水平知之甚少。为了表征小鼠模型以及人类中的抗茎部体液应答，在血清学测定中采用我们组先前开发的嵌合血凝素构建体。而流感病毒感染诱导高滴度的茎反应性抗体，免疫灭活流感病毒疫苗未能做到这一点，在小鼠模型。从感染流感病毒的人类个体收集的血清样品的分析也揭示了茎反应性抗体的诱导。最后，我们表明，在小鼠和人类中诱导的血凝素茎定向抗体在体外和体内具有广泛的反应性和中和活性。研究结果表明，2组血凝素的茎结构域中存在高度保守的表位，这些表位可以作为开发人类通用流感病毒疫苗的目标。
Broadly neutralizing antibodies directed against the conserved stalk domain of the viral hemagglutinin have attracted increasing attention in recent years. However, only a limited number of stalk antibodies directed against group 2 influenza hemagglutinins have been isolated so far. Also, little is known about the general level of induction of these antibodies by influenza virus vaccination or infection. To characterize the anti-stalk humoral response in the mouse model as well as in humans, chimeric hemagglutinin constructs previously developed in our group were employed in serological assays. Whereas influenza virus infection induced high titers of stalk-reactive antibodies, immunization with inactivated influenza virus vaccines failed to do so in the mouse model. Analysis of serum samples collected from human individuals who were infected by influenza viruses also revealed the induction of stalk-reactive antibodies. Finally, we show that the hemagglutinin stalk-directed antibodies induced in mice and humans have broad reactivity and neutralizing activity in vitro and in vivo. The results of the study point toward the existence of highly conserved epitopes in the stalk domains of group 2 hemagglutinins, which can be targeted for the development of a universal influenza virus vaccine in humans.