Polyclonal epitope mapping reveals temporal dynamics and diversity of human antibody responses to H5N1 vaccination.
Polyclonal epitope mapping reveals temporal dynamics and diversity of human antibody responses to H5N1 vaccination.
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DOI：
10.1016/j.celrep.2020.108682
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发表时间：
2021-01-26
期刊：
影响因子：
8.8
通讯作者：
Ward AB
中科院分区：
文献类型：
--
作者：
Han J;Schmitz AJ;Richey ST;Dai YN;Turner HL;Mohammed BM;Fremont DH;Ellebedy AH;Ward AB
新型甲型流感病毒（IAV）毒株可引发对保守表位的记忆免疫反应，使其成为通用流感病毒疫苗的有利抗原选择。评估这些免疫原需要全面了解多克隆抗体 (pAb) 反应所针对的抗原位点，单颗粒电子显微镜 (EM) 可以灵敏地检测到该抗原位点。在这项研究中，我们采用 EM 多克隆表位作图 (EMPEM) 来广泛表征人类 H5N1 免疫后 pAb 对血凝素 (HA) 的反应。源自记忆 B 细胞的交叉反应性 pAb 立即与 HA 茎结合，并在接种疫苗后持续存在一年多。相比之下，针对HA头部多个位点的从头pAb反应，针对先前确定的H5 HA上的关键中和位点，在第二次免疫后扩大并迅速减弱。因此，EMPEM 提供了一个强大的工具，用于全面跟踪新型通用流感疫苗候选物引起的免疫反应的特异性和持久性。含有 H5N1 等新型流感毒株的疫苗是增强人类广泛交叉反应性抗体反应的有希望的候选疫苗。韩等人。随着时间的推移，从结构上表征人类群体中 H5N1 疫苗接种后的免疫力，识别出针对 H5N1 中和位点或与其他流感病毒发生交叉反应的多克隆抗体。
Novel influenza A virus (IAV) strains elicit recall immune responses to conserved epitopes, making them favorable antigenic choices for universal influenza virus vaccines. Evaluating these immunogens requires a thorough understanding of the antigenic sites targeted by the polyclonal antibody (pAb) response, which single-particle electron microscopy (EM) can sensitively detect. In this study, we employ EM polyclonal epitope mapping (EMPEM) to extensively characterize the pAb response to hemagglutinin (HA) after H5N1 immunization in humans. Cross-reactive pAbs originating from memory B cells immediately bound the stem of HA and persisted for more than a year after vaccination. In contrast, de novo pAb responses to multiple sites on the head of HA, targeting previously determined key neutralizing sites on H5 HA, expanded after the second immunization and waned quickly. Thus, EMPEM provides a robust tool for comprehensively tracking the specificity and durability of immune responses elicited by novel universal influenza vaccine candidates. Vaccines containing novel influenza strains such as H5N1 are promising candidates for boosting broadly cross-reactive antibody responses in humans. Han et al. structurally characterize immunity after H5N1 vaccination in a human cohort over time, identifying polyclonal antibodies that target neutralizing sites on H5N1 or cross-react with other influenza viruses.
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影响因子：
7.3
作者：
Sun J;Kudahl UJ;Simon C;Cao Z;Reinherz EL;Brusic V
通讯作者：
Brusic V
影响因子：
17.1
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
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Wilson PC
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
168.9
作者：
Claas, ECJ;Osterhaus, ADME;Webster, RG
通讯作者：
Webster, RG
DOI：
10.1073/pnas.1414070111
发表时间：
2014-09-09
影响因子：
11.1
作者：
Ellebedy, Ali H.;Krammer, Florian;Ahmed, Rafi
通讯作者：
Ahmed, Rafi