Profiling Germinal Center-like B Cell Responses to Conjugate Vaccines Using Synthetic Immune Organoids.
Profiling Germinal Center-like B Cell Responses to Conjugate Vaccines Using Synthetic Immune Organoids.
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DOI：
10.1021/acscentsci.2c01473
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发表时间：
2023-04-26
影响因子：
18.2
通讯作者：
Singh, Ankur
中科院分区：
文献类型：
--
作者：
Moeller, Tyler D.;Shah, Shivem B.;Lai, Kristine;Lopez-Barbosa, Natalia;Desai, Primit;Wang, Weiyao;Zhong, Zhe;Redmond, David;DeLisa, Matthew P.;Singh, Ankur
糖工程化细菌已经成为一种具有成本效益的平台，用于快速和可控的生物合成设计师缀合物疫苗。然而，很少有人知道这种共轭物与幼稚B细胞的接合，以诱导生发中心（GC）的形成，生发中心是一种亚解剖微环境，将幼稚B细胞转化为分泌抗体的浆细胞。使用基于三维生物材料的B细胞滤泡类器官系统，我们证明了缀合物触发了标志性GC标记物、B细胞受体聚集、细胞内信号传导和体细胞超突变的稳健表达。这些反应依赖于偶联物的相对免疫原性，并与体内体液反应相关。这些机制的发生被用于在显著短于典型的基于动物免疫的工作流程的时间尺度上发现针对缀合物组分的高亲和力抗体。总的来说，这些发现突出了合成类器官用于快速预测缀合物疫苗功效以及加速抗原特异性抗体发现的潜力。在这里，我们设计了小鼠B细胞滤泡类器官，以了解糖缀合物疫苗候选物对B细胞成熟的影响，并鉴定高亲和力抗原特异性抗体。
Glycoengineered bacteria have emerged as a cost-effective platform for rapid and controllable biosynthesis of designer conjugate vaccines. However, little is known about the engagement of such conjugates with naïve B cells to induce the formation of germinal centers (GC), a subanatomical microenvironment that converts naïve B cells into antibody-secreting plasma cells. Using a three-dimensional biomaterials-based B-cell follicular organoid system, we demonstrate that conjugates triggered robust expression of hallmark GC markers, B cell receptor clustering, intracellular signaling, and somatic hypermutation. These responses depended on the relative immunogenicity of the conjugate and correlated with the humoral response in vivo. The occurrence of these mechanisms was exploited for the discovery of high-affinity antibodies against components of the conjugate on a time scale that was significantly shorter than for typical animal immunization-based workflows. Collectively, these findings highlight the potential of synthetic organoids for rapidly predicting conjugate vaccine efficacy as well as expediting antigen-specific antibody discovery. Here, we engineered mouse B cell follicle organoids to understand the impact of glycoconjugate vaccine candidates on B cell maturation and to identify high-affinity antigen-specific antibodies.
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影响因子：
64.5
作者：
BEREK, C;BERGER, A;APEL, M
通讯作者：
APEL, M
DOI：
10.1038/nri3804
发表时间：
2015-03
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.1
作者：
Fernandez, Stefan;Palmer, Dupeh R.;Sun, Wellington
通讯作者：
Sun, Wellington
影响因子：
16.6
作者：
Béguelin W;Rivas MA;Calvo Fernández MT;Teater M;Purwada A;Redmond D;Shen H;Challman MF;Elemento O;Singh A;Melnick AM
通讯作者：
Melnick AM
影响因子：
14.9
作者：
GIANNINI, G;RAPPUOLI, R;RATTI, G
通讯作者：
RATTI, G