Integrated single-cell analysis revealed immune dynamics during Ad5-nCoV immunization.
Integrated single-cell analysis revealed immune dynamics during Ad5-nCoV immunization.
复制标题
综合单细胞分析揭示了 Ad5-nCoV 免疫过程中的免疫动态
DOI：
10.1038/s41421-021-00300-2
复制
发表时间：
2021-08-10
期刊：
影响因子：
33.5
通讯作者：
Wen W
中科院分区：
文献类型：
--
作者：
Cao Q;Wu S;Xiao C;Chen S;Chi X;Cui X;Tang H;Su W;Zheng Y;Zhong J;Li Z;Li F;Chen H;Hou L;Wang H;Wen W
由SARS-CoV-2驱动的冠状病毒病2019年(新冠肺炎)是一种严重的传染病，已成为全球健康威胁。疫苗是抗击新冠肺炎最有效的公共卫生工具之一。免疫状态对于评估疫苗的安全性和反应至关重要，然而，免疫过程中免疫反应的演变仍然知之甚少。单细胞RNA测序(scRNA-seq)是研究多细胞行为和发现治疗性抗体的有力工具。在这里，通过对四名新冠肺炎疫苗试验参与者在免疫期间纵向的外周血单核细胞进行scRNA/V(D)J-seq，我们揭示了协同的和细胞类型特异性的干扰素反应增强了细胞免疫，以及SARS-CoV-2特异性抗体增强了体液免疫。基于CDR3序列和种系扩增，我们能够鉴定出几种潜在的结合抗体。我们从已鉴定的谱系中合成、表达和检测了21个克隆。其中，单抗P3V6-1与S蛋白胞外区具有较高的亲和力，有望成为新冠肺炎的治疗试剂。总体而言，我们的发现为通过新的scRNA/V(D)J-seq方法评估疫苗提供了见解，这可能有助于开发更有效、更持久和更安全的预防性疫苗。
Coronavirus disease 2019 (COVID-19), driven by SARS-CoV-2, is a severe infectious disease that has become a global health threat. Vaccines are among the most effective public health tools for combating COVID-19. Immune status is critical for evaluating the safety and response to the vaccine, however, the evolution of the immune response during immunization remains poorly understood. Single-cell RNA sequencing (scRNA-seq) represents a powerful tool for dissecting multicellular behavior and discovering therapeutic antibodies. Herein, by performing scRNA/V(D)J-seq on peripheral blood mononuclear cells from four COVID-19 vaccine trial participants longitudinally during immunization, we revealed enhanced cellular immunity with concerted and cell type-specific IFN responses as well as boosted humoral immunity with SARS-CoV-2-specific antibodies. Based on the CDR3 sequence and germline enrichment, we were able to identify several potential binding antibodies. We synthesized, expressed and tested 21 clones from the identified lineages. Among them, one monoclonal antibody (P3V6-1) exhibited relatively high affinity with the extracellular domain of Spike protein, which might be a promising therapeutic reagent for COVID-19. Overall, our findings provide insights for assessing vaccine through the novel scRNA/V(D)J-seq approach, which might facilitate the development of more potent, durable and safe prophylactic vaccines.
登录
查看更多内容
影响因子：
64.5
作者：
Daniloski Z;Jordan TX;Wessels HH;Hoagland DA;Kasela S;Legut M;Maniatis S;Mimitou EP;Lu L;Geller E;Danziger O;Rosenberg BR;Phatnani H;Smibert P;Lappalainen T;tenOever BR;Sanjana NE
通讯作者：
Sanjana NE
影响因子：
39.2
作者：
Baden LR;Karita E;Mutua G;Bekker LG;Gray G;Page-Shipp L;Walsh SR;Nyombayire J;Anzala O;Roux S;Laher F;Innes C;Seaman MS;Cohen YZ;Peter L;Frahm N;McElrath MJ;Hayes P;Swann E;Grunenberg N;Grazia-Pau M;Weijtens M;Sadoff J;Dally L;Lombardo A;Gilmour J;Cox J;Dolin R;Fast P;Barouch DH;Laufer DS;B003-IPCAVD004-HVTN091 Study Group
通讯作者：
B003-IPCAVD004-HVTN091 Study Group
影响因子：
64.8
作者：
Hansen, Scott G.;Ford, Julia C.;Lewis, Matthew S.;Ventura, Abigail B.;Hughes, Colette M.;Coyne-Johnson, Lia;Whizin, Nathan;Oswald, Kelli;Shoemaker, Rebecca;Swanson, Tonya;Legasse, Alfred W.;Chiuchiolo, Maria J.;Parks, Christopher L.;Axthelm, Michael K.;Nelson, Jay A.;Jarvis, Michael A.;Piatak, Michael, Jr.;Lifson, Jeffrey D.;Picker, Louis J.
通讯作者：
Picker, Louis J.
影响因子：
14.8
作者：
Chovanec, Peter;Bolland, Daniel J.;Corcoran, Anne E.
通讯作者：
Corcoran, Anne E.
影响因子：
4.8
作者：
Ewer K;Sebastian S;Spencer AJ;Gilbert S;Hill AVS;Lambe T
通讯作者：
Lambe T