Self-assembling synthetic nanoadjuvant scaffolds cross-link B cell receptors and represent new platform technology for therapeutic antibody production.
Self-assembling synthetic nanoadjuvant scaffolds cross-link B cell receptors and represent new platform technology for therapeutic antibody production.
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DOI：
10.1126/sciadv.abj1691
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发表时间：
2021-08
期刊：
影响因子：
13.6
通讯作者：
Mallapragada SK
中科院分区：
文献类型：
--
作者：
Senapati S;Darling RJ;Ross KA;Wannemeuhler MJ;Narasimhan B;Mallapragada SK
自组装纳米佐剂支架使B细胞受体交联，是一种新的治疗性抗体平台技术。宿主抗体反应对于提供对感染性病原体的保护至关重要。我们开创了一种基于五嵌段共聚物的新型自组装胶束，与传统佐剂相比，这种胶束可以增强抗体反应，同时提供低炎症环境。这种“恰到好处”的免疫反应在老年人疫苗的合理设计中至关重要。在这里，我们报道了五嵌段共聚物胶束增强抗体反应的机制，与其他形成胶束的合成嵌段共聚物不同，五嵌段共聚物胶束作为抗原呈递给B细胞和交联型B细胞受体的支架。我们利用这一独特的机制，开发了这些支架作为一种平台技术，在体外产生抗体。我们表明，这种新的方法可以用来产生实验室规模的针对多种抗原的治疗性抗体，包括那些与SARS-CoV-2和鼠疫杆菌相关的抗体，进一步扩大这些纳米材料的价值，以快速开发针对传染病的对策。
Self-assembling nanoadjuvant scaffolds cross-link B cell receptors and are a new platform technology for therapeutic antibodies. Host antibody responses are pivotal for providing protection against infectious agents. We have pioneered a new class of self-assembling micelles based on pentablock copolymers that enhance antibody responses while providing a low inflammatory environment compared to traditional adjuvants. This type of “just-right” immune response is critical in the rational design of vaccines for older adults. Here, we report on the mechanism of enhancement of antibody responses by pentablock copolymer micelles, which act as scaffolds for antigen presentation to B cells and cross-link B cell receptors, unlike other micelle-forming synthetic block copolymers. We exploited this unique mechanism and developed these scaffolds as a platform technology to produce antibodies in vitro. We show that this novel approach can be used to generate laboratory-scale quantities of therapeutic antibodies against multiple antigens, including those associated with SARS-CoV-2 and Yersinia pestis, further expanding the value of these nanomaterials to rapidly develop countermeasures against infectious diseases.
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