Molecular-level analysis of the serum antibody repertoire in young adults before and after seasonal influenza vaccination.
Molecular-level analysis of the serum antibody repertoire in young adults before and after seasonal influenza vaccination.
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DOI：
10.1038/nm.4224
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发表时间：
2016-12
期刊：
影响因子：
82.9
通讯作者：
Georgiou G
中科院分区：
文献类型：
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作者：
Lee J;Boutz DR;Chromikova V;Joyce MG;Vollmers C;Leung K;Horton AP;DeKosky BJ;Lee CH;Lavinder JJ;Murrin EM;Chrysostomou C;Hoi KH;Tsybovsky Y;Thomas PV;Druz A;Zhang B;Zhang Y;Wang L;Kong WP;Park D;Popova LI;Dekker CL;Davis MM;Carter CE;Ross TM;Ellington AD;Wilson PC;Marcotte EM;Mascola JR;Ippolito GC;Krammer F;Quake SR;Kwong PD;Georgiou G
对流感血清学免疫的分子理解被人类多克隆抗体应答的复杂性所混淆。在这里，我们使用免疫球蛋白的高分辨率蛋白质组学分析（称为Ig-seq），结合编码B细胞受体的转录本的高通量测序（BCR-seq），以定量确定在接种三价季节性流感疫苗前后年轻人血清中个体克隆型水平的抗体库。血清库包括40至147个克隆型，这些克隆型对三价流感疫苗的三种单价组分中的每一种具有特异性，其中加强的预先存在的克隆型占应答的约60%。出乎意料的高分数的血清抗体识别H1和H3单价疫苗。这些H1 + H3交叉反应性抗体的重组版本显示出与来自先前循环病毒株的血凝素（HA）的广泛结合;这些抗体中的几种在多个供体的血清中普遍存在，识别HA头部结构域中的相同保守表位。尽管HA-头特异性H1 + H3抗体在体外没有显示出中和活性，但当在攻击之前或之后施用时，它们保护小鼠免受H1N1和H3 N2病毒株的感染。总的来说，我们的数据揭示了关于流感疫苗接种的血清学反应的意想不到的见解，并提出了关于使用四价疫苗而不是三价疫苗的额外益处的问题。
Molecular understanding of serological immunity to influenza has been confounded by the complexity of the polyclonal antibody response in humans. Here we used high-resolution proteomics analysis of immunoglobulin (referred to as Ig-seq) coupled with high-throughput sequencing of transcripts encoding B cell receptors (BCR-seq) to quantitatively determine the antibody repertoire at the individual clonotype level in the sera of young adults before and after vaccination with trivalent seasonal influenza vaccine. The serum repertoire comprised between 40 and 147 clonotypes that were specific to each of the three monovalent components of the trivalent influenza vaccine, with boosted pre-existing clonotypes accounting for ~60% of the response. An unexpectedly high fraction of serum antibodies recognized both the H1 and H3 monovalent vaccines. Recombinant versions of these H1 + H3 cross-reactive antibodies showed broad binding to hemagglutinins (HAs) from previously circulating virus strains; several of these antibodies, which were prevalent in the serum of multiple donors, recognized the same conserved epitope in the HA head domain. Although the HA-head-specific H1 + H3 antibodies did not show neutralization activity in vitro, they protected mice against infection with the H1N1 and H3N2 virus strains when administered before or after challenge. Collectively, our data reveal unanticipated insights regarding the serological response to influenza vaccination and raise questions about the added benefits of using a quadrivalent vaccine instead of a trivalent vaccine.