A mammalian cell display system for the characterisation and evolution of neutralising antibodies

中和抗体反应是抗病毒免疫的关键组成部分。然而，大多数用于鉴定病原体特异性抗体的高通量筛选平台依赖于抗原结合亲和力，其不基于中和潜力进行区分。因此，非中和抗体通常由此类管线产生。为了促进中和抗体的鉴定，我们的目标是开发一种哺乳动物细胞展示平台，其中通过保护性抗体的表面呈递来屏蔽细胞免受感染。这将与下一代测序相结合，将表型与基因型联系起来，从而快速鉴定和表征治疗相关的nAb候选物。在鉴定之后，我们的目标是利用分子病毒学、定向进化和结构生物学的结合来扩大我们对这些nAb的中和特性的理解。BBSRC优先领域这个项目主要属于“生物科学技术开发”BBSRC优先领域，但也有助于“动物研究中的替代、改进和减少”。它还结合了合成生物学的思想，特别是定向进化和蛋白质工程。

The neutralising antibody response is a key component of antiviral immunity. However, most high-throughput screening platforms for identification of pathogen-specific antibodies rely on antigen binding affinity, which does not discriminate on the basis of neutralisation potential.Consequently, non-neutralising antibodies are commonly produced from such pipelines. To facilitate identification of neutralising antibodies we aim to develop a mammalian cell display platform in which cells are shielded from infection by surface presentation of protective antibodies. This will be combined with next-generation sequencing to link phenotype to genotype, allowing the rapid identification and characterisation of therapeutically-relevant nAb candidates. Following identification, we aim to expand our understanding of these nAb's neutralising properties using a combination of molecular virology, directed evolution and structural biology.BBSRC priority areasThis project primarily comes under the 'technology development for the biosciences' BBSRCpriority area, but also contributes to the 'replacement, refinement and reduction of animalsin research (3Rs)'. It furthermore incorporates ideas from synthetic biology, in particulardirected evolution and protein engineering.