Author:
Hurtado Jonathan,Flynn Claudia,Lee Jeong Hyun,Salcedo Eugenia C.,Cottrell Christopher A.,Skog Patrick D.,Burton Dennis R.,Nemazee David,Schief William R.,Landais Elise,Sok Devin,Briney Bryan
Abstract
The ability to efficiently isolate antigen-specific B cells in high throughput will greatly accelerate the discovery of therapeutic monoclonal antibodies (mAbs) and catalyze rational vaccine development. Traditional mAb discovery is a costly and labor-intensive process, although recent advances in single-cell genomics using emulsion microfluidics allow simultaneous processing of thousands of individual cells. Here we present a streamlined method for isolation and analysis of large numbers of antigen-specific B cells, including next generation antigen barcoding and an integrated computational framework for B cell multi-omics. We demonstrate the power of this approach by recovering thousands of antigen-specific mAbs, including the efficient isolation of extremely rare precursors of VRC01-class and IOMA-class broadly neutralizing HIV mAbs.
Funder
National Institute of Allergy and Infectious Diseases
National Institute of General Medical Sciences
International AIDS Vaccine Initiative
Subject
Infectious Diseases,Microbiology (medical),Immunology,Microbiology