Immune history profoundly affects broadly protective B cell responses to influenza.
Immune history profoundly affects broadly protective B cell responses to influenza.
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DOI：
10.1126/scitranslmed.aad0522
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发表时间：
2015-12-02
影响因子：
17.1
通讯作者：
Wilson PC
中科院分区：
文献类型：
--
作者：
Andrews SF;Huang Y;Kaur K;Popova LI;Ho IY;Pauli NT;Henry Dunand CJ;Taylor WM;Lim S;Huang M;Qu X;Lee JH;Salgado-Ferrer M;Krammer F;Palese P;Wrammert J;Ahmed R;Wilson PC
生产具有广泛保护性的流感疫苗对全球健康至关重要。了解免疫记忆如何影响流感免疫力是实现这一目标的关键。我们连续几年对B细胞对2009年H1N1流感疫苗的反应进行了深入研究。对疫苗诱导的浆母细胞产生的单克隆抗体的分析表明，对疫苗接种菌株具有低血清学滴度的个体产生了广泛反应性、HA茎偏性反应。更高的预先存在的血清抗体水平与菌株特异性HA头部主导的反应。我们证明，这种HA头部免疫优势包括HA茎表位的可及性差。此外，我们显示了HA茎反应性抗体的多反应性，这可能导致这些细胞的反选择。因此，针对HA头部表位的预先存在的记忆占主导地位，在用类似菌株再接种后抑制针对HA茎部的广泛保护性应答。考虑流感暴露史对于旨在引发广泛中和抗体的新疫苗策略至关重要。
Generating a broadly protective influenza vaccine is critical to global health. Understanding how immune memory influences influenza immunity is central to this goal. We undertook an in-depth study of the B cell response to the pandemic 2009 H1N1 vaccine over consecutive years. Analysis of monoclonal Abs generated from vaccine-induced plasmablasts demonstrated that individuals with low preexisting serological titers to the vaccinating strain generated a broadly reactive, HA stalk-biased, response. Higher preexisting serum antibody levels correlated with a strain-specific HA head-dominated response. We demonstrate that this HA head immunodominance encompasses poor accessibility of the HA stalk epitopes. Further, we show polyreactivity of HA stalk-reactive antibodies that could cause counterselection of these cells. Thus, preexisting memory against HA head epitopes predominate, inhibiting a broadly protective response against the HA stalk upon revaccination with similar strains. Consideration of influenza exposure history is critical for new vaccine strategies designed to elicit broadly neutralizing antibodies.