Guiding the Immune Response against Influenza Virus Hemagglutinin toward the Conserved Stalk Domain by Hyperglycosylation of the Globular Head Domain
Guiding the Immune Response against Influenza Virus Hemagglutinin toward the Conserved Stalk Domain by Hyperglycosylation of the Globular Head Domain
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DOI：
10.1128/jvi.02608-13
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发表时间：
2014-01-01
影响因子：
5.4
通讯作者：
Palese, Peter
中科院分区：
文献类型：
--
作者：
Eggink, Dirk;Goff, Peter H.;Palese, Peter
流感病毒血凝素由一个高度可变且免疫显性的头部结构域和一个更为保守但免疫亚显性的茎部结构域组成。我们在血凝素头部结构域引入了7个N - 连接糖基化位点，以遮蔽免疫显性的抗原位点。高糖基化的血凝素在免疫小鼠中增强了针对茎部的血清反应性，同时减弱了针对头部的反应。在受到流感病毒攻击时，接种高糖基化血凝素的小鼠比接种野生型血凝素的小鼠在预防发病和死亡方面受到更好的保护。
Influenza virus hemagglutinin consists of a highly variable and immunodominant head domain and a more conserved but immunosubdominant stalk domain. We introduced seven N-linked glycosylation sites in the hemagglutinin head domain to shield the immunodominant antigenic sites. The hyperglycosylated hemagglutinin enhanced stalk-directed seroreactivity while dampening the head response in immunized mice. Upon influenza virus challenge, mice vaccinated with the hyperglycosylated hemagglutinin were better protected against morbidity and mortality than mice receiving the wild-type hemagglutinin.