Multi-Donor Longitudinal Antibody Repertoire Sequencing Reveals the Existence of Public Antibody Clonotypes in HIV-1 Infection.
Multi-Donor Longitudinal Antibody Repertoire Sequencing Reveals the Existence of Public Antibody Clonotypes in HIV-1 Infection.
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DOI：
10.1016/j.chom.2018.05.001
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发表时间：
2018-06-13
影响因子：
30.3
通讯作者：
Georgiev IS
中科院分区：
文献类型：
--
作者：
Setliff I;McDonnell WJ;Raju N;Bombardi RG;Murji AA;Scheepers C;Ziki R;Mynhardt C;Shepherd BE;Mamchak AA;Garrett N;Karim SA;Mallal SA;Crowe JE Jr;Morris L;Georgiev IS
感染个体内单一抗体谱系的表征为 Env 特异性抗体的开发提供了见解。然而，对 HIV-1 体液反应的系统水平理解有限。在这里，我们使用下一代测序技术询问了多个感染艾滋病毒的捐献者的抗体库，从感染初始状态到急性和慢性感染。这项分析揭示了多个艾滋病毒感染者共享的“公共”抗体克隆型的存在。确认了三位捐赠者共享的已识别公共克隆型的代表性抗体的 HIV-1 反应性。此外，对公开的抗体库测序数据集的荟萃分析显示，抗体与已知的 HIV 反应性抗体具有高度序列同一性，即使是在据报道未感染 HIV 的抗体库中也是如此。 HIV感染者中公共抗体克隆型的发现为更好地了解HIV-1感染的抗体反应以及克隆型特异性疫苗的开发提供了一条巨大潜力的途径。通过 NGS 分析了供者内针对 HIV-1 感染的纵向抗体库 发现了多个 HIV 感染者共享的公共抗体克隆型 三个供者共享的公共抗体克隆型被证实具有 HIV 反应性 来自 HIV 初治抗体库的抗体序列与已知的 HIV 抗体相似 HIV 感染者的总体抗体库 被认为是独一无二的。塞特利夫等人。分析 HIV-1 感染者的纵向抗体库，以揭示多个受试者中是否存在“公共”HIV 反应性抗体。即使在未接触过 HIV 的抗体库中，也鉴定出了与已知 HIV 反应性抗体具有高度同一性的抗体序列。
Characterization of single antibody lineages within infected individuals has provided insights into the development of Env-specific antibodies. However, a systems-level understanding of the humoral response against HIV-1 is limited. Here, we interrogated the antibody repertoires of multiple HIV-infected donors from an infection-naive state through acute and chronic infection using next-generation sequencing. This analysis revealed the existence of “public” antibody clonotypes that were shared among multiple HIV-infected individuals. The HIV-1 reactivity for representative antibodies from an identified public clonotype shared by three donors was confirmed. Furthermore, a meta-analysis of publicly available antibody repertoire sequencing datasets revealed antibodies with high sequence identity to known HIV-reactive antibodies, even in repertoires that were reported to be HIV naive. The discovery of public antibody clonotypes in HIV-infected individuals represents an avenue of significant potential for better understanding antibody responses to HIV-1 infection, as well as for clonotype-specific vaccine development. Within-donor longitudinal antibody repertoire to HIV-1 infection was analyzed by NGS Public antibody clonotypes shared among multiple HIV-infected individuals were uncovered A public antibody clonotype shared by three donors was confirmed to be HIV reactive Antibody sequences from HIV-naive repertoires are similar to known HIV antibodies The overall antibody repertoires of HIV-infected subjects are considered to be unique. Setliff et al. analyze the longitudinal antibody repertoire of HIV-1-infected individuals to uncover the existence of “public” HIV-reactive antibodies in multiple subjects. Antibody sequences with high identity to known HIV-reactive antibodies were identified even in HIV-naive repertoires.
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影响因子：
30.3
作者：
Jackson KJ;Liu Y;Roskin KM;Glanville J;Hoh RA;Seo K;Marshall EL;Gurley TC;Moody MA;Haynes BF;Walter EB;Liao HX;Albrecht RA;García-Sastre A;Chaparro-Riggers J;Rajpal A;Pons J;Simen BB;Hanczaruk B;Dekker CL;Laserson J;Koller D;Davis MM;Fire AZ;Boyd SD
通讯作者：
Boyd SD
影响因子：
5.4
作者：
Acharya, Priyamvada;Tolbert, William D.;Pazgier, Marzena
通讯作者：
Pazgier, Marzena
影响因子：
5.8
作者：
Dunbar, James;Deane, Charlotte M.
通讯作者：
Deane, Charlotte M.
影响因子：
6.2
作者：
Crowe, James E., Jr.;Koff, Wayne C.
通讯作者：
Koff, Wayne C.
影响因子：
8.6
作者：
DeFalco, Jeff;Harbell, Michael;Robinson, William H.
通讯作者：
Robinson, William H.