Immune history shapes specificity of pandemic H1N1 influenza antibody responses.
Immune history shapes specificity of pandemic H1N1 influenza antibody responses.
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DOI：
10.1084/jem.20130212
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发表时间：
2013-07-29
期刊：
影响因子：
--
通讯作者：
Hensley SE
中科院分区：
文献类型：
--
作者：
Li Y;Myers JL;Bostick DL;Sullivan CB;Madara J;Linderman SL;Liu Q;Carter DM;Wrammert J;Esposito S;Principi N;Plotkin JB;Ross TM;Ahmed R;Wilson PC;Hensley SE
H1N1抗体反应的特异性可以转移到HA受体结合结构域附近的表位后，连续感染病毒株，共享同源性在这个区域。针对2009年大流行性H1N1（pH1N1）病毒的人抗体应答主要针对血凝素（HA）蛋白的茎和受体结合结构域中的保守表位。这与雪貂中产生的pH1N1抗体应答形成鲜明对比，雪貂中产生的pH1N1抗体应答集中在HA的可变Sa抗原位点。在这里，我们表明，大多数人之间出生的1983年和1996年引起的pH1N1抗体反应，针对HA受体结合域附近的表位。重要的是，1983年之前或1996年之后出生的大多数个体不会引发针对该HA表位的pH1N1抗体。在1983年至1996年之间流行的大多数季节性H1N1（sH1N1）病毒的HA在该HA表位中具有关键的K133氨基酸，而在1983年之前或1996年之后流行的大多数sH1N1病毒中，该氨基酸突变或缺失。我们先后用1991年的sH1N1病毒和pH1N1病毒感染雪貂。从这些动物分离的血清针对涉及氨基酸K133的HA表位。这些数据表明，pH1N1抗体反应的特异性可以转移到HA受体结合结构域附近的表位后，连续感染sH1N1和pH1N1病毒，共享同源性在这个区域。
The specificity of H1N1 antibody responses can be shifted to epitopes near the HA receptor–binding domain after sequential infections with viral strains that share homology in this region. Human antibody responses against the 2009 pandemic H1N1 (pH1N1) virus are predominantly directed against conserved epitopes in the stalk and receptor-binding domain of the hemagglutinin (HA) protein. This is in stark contrast to pH1N1 antibody responses generated in ferrets, which are focused on the variable Sa antigenic site of HA. Here, we show that most humans born between 1983 and 1996 elicited pH1N1 antibody responses that are directed against an epitope near the HA receptor–binding domain. Importantly, most individuals born before 1983 or after 1996 did not elicit pH1N1 antibodies to this HA epitope. The HAs of most seasonal H1N1 (sH1N1) viruses that circulated between 1983 and 1996 possess a critical K133 amino acid in this HA epitope, whereas this amino acid is either mutated or deleted in most sH1N1 viruses circulating before 1983 or after 1996. We sequentially infected ferrets with a 1991 sH1N1 virus and then a pH1N1 virus. Sera isolated from these animals were directed against the HA epitope involving amino acid K133. These data suggest that the specificity of pH1N1 antibody responses can be shifted to epitopes near the HA receptor–binding domain after sequential infections with sH1N1 and pH1N1 viruses that share homology in this region.
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作者：
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发表时间：
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