Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
J Virol. 2013 Apr;87(8):4728-37. doi: 10.1128/JVI.03509-12. Epub 2013 Feb 13.
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.
近年来，针对病毒血凝素保守茎部的广谱中和抗体引起了越来越多的关注。然而，迄今为止，仅分离到少数针对 2 类流感血凝素的茎部抗体。此外，人们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。为了在小鼠模型以及人类中描述抗茎部体液免疫反应，我们小组先前开发的嵌合血凝素构建体被用于血清学检测。虽然流感病毒感染诱导了高滴度的茎反应性抗体，但在小鼠模型中，灭活流感病毒疫苗免疫未能诱导产生这种抗体。对感染流感病毒的人类个体采集的血清样本进行分析，也揭示了茎反应性抗体的诱导。最后，我们证明在小鼠和人类中诱导的血凝素茎部定向抗体在体外和体内具有广泛的反应性和中和活性。该研究的结果表明，2 类血凝素茎部存在高度保守的表位，可针对人类开发通用流感病毒疫苗。
