An Egg-Derived Sulfated N-Acetyllactosamine Glycan Is an Antigenic Decoy of Influenza Virus Vaccines.
An Egg-Derived Sulfated N-Acetyllactosamine Glycan Is an Antigenic Decoy of Influenza Virus Vaccines.
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DOI：
10.1128/mbio.00838-21
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发表时间：
2021-06-29
期刊：
影响因子：
6.4
通讯作者：
Wilson PC
中科院分区：
文献类型：
--
作者：
Guthmiller JJ;Utset HA;Henry C;Li L;Zheng NY;Sun W;Costa Vieira M;Zost S;Huang M;Hensley SE;Cobey S;Palese P;Wilson PC
为了生产疫苗而在鸡蛋中生长的流感病毒通常在鸡蛋适应过程中获得突变，或者具有与在人类中传播的病毒不同的糖基化模式。在这里，我们报告说，季节性流感病毒疫苗具有鸡蛋衍生的聚糖，这是一个抗原诱饵，与鸡蛋结合单克隆抗体与硫酸化N-乙酰乳糖胺（LacNAc）反应。接受鸡蛋生长疫苗的受试者中有一半对这种鸡蛋衍生抗原产生了抗体反应。结合鸡蛋的单克隆抗体特异性结合鸡蛋中生长的病毒，但不结合其他鸡源性细胞中生长的病毒，这表明只有鸡蛋生长的疫苗才能诱导抗鸡蛋抗体。值得注意的是，针对卵抗原的抗体利用了有限的抗体库并具有天然抗体的特征，因为大多数抗体是IgM并具有简单的重链互补决定区3。通过分析流感病毒疫苗诱导的浆母细胞的公共数据集，我们发现了在研究中共享的卵结合公共克隆型。总之，这项研究表明，鸡蛋生长的疫苗可以诱导针对鸡蛋相关聚糖的抗体，这可能会转移宿主的免疫反应远离保护性表位。
Influenza viruses grown in eggs for the purposes of vaccine generation often acquire mutations during egg adaptation or possess different glycosylation patterns than viruses circulating among humans. Here, we report that seasonal influenza virus vaccines possess an egg-derived glycan that is an antigenic decoy, with egg-binding MAbs reacting with a sulfated N-acetyllactosamine (LacNAc). Half of subjects that received an egg-grown vaccine mounted an antibody response against this egg-derived antigen. Egg-binding monoclonal antibodies specifically bind viruses grown in eggs, but not viruses grown in other chicken-derived cells, suggesting that only egg-grown vaccines can induce antiegg antibodies. Notably, antibodies against the egg antigen utilized a restricted antibody repertoire and possessed features of natural antibodies, as most antibodies were IgM and had a simple heavy-chain complementarity-determining region 3. By analyzing a public data set of influenza virus vaccine-induced plasmablasts, we discovered egg-binding public clonotypes that were shared across studies. Together, this study shows that egg-grown vaccines can induce antibodies against an egg-associated glycan, which may divert the host immune response away from protective epitopes.