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

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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.