Antibody discovery through post-vaccination single-cell transcriptomics and haplotype-resolved germline sequencing

Abstract This study leverages the unique capabilities of nanopore sequencing to facilitate de novo antibody discovery, integrating full-length single B cell transcriptomics with haplotype-resolved germline assemblies. Utilizing nanopore technology, we achieved highly accurate sequencing of the immunoglobulin (IG) loci, capturing the IG heavy chain locus in a fully phased contig that delineates the maternal and paternal contributions to the antibody repertoire. Following a measles, mumps, and rubella (MMR) vaccination, we collected B cells and performed single-cell transcriptome sequencing, yielding precise consensus sequences for somatically rearranged and hypermutated light and heavy chain IG transcripts. The high fidelity of nanopore sequencing enabled the generation of a diverse array of antibody candidates, several of which demonstrated binding to measles antigens and effective neutralization of the live virus. This research underscores the transformative potential of nanopore sequencing in enhancing our understanding of antibody diversity and advancing therapeutic antibody development, providing a robust framework for innovative strategies in immunology and vaccine design. Biography Scott Hickey is the Director of Commercial Applications at Oxford Nanopore Technologies, based in San Francisco, CA. His team runs pilot projects demonstrating the impact of Oxford Nanopore sequencing in rare disease, cancer, single cell, epigenetics, and metagenomics with sequencing and analysis expertise using the latest protocols and bioinformatics workflows. Scott received his PhD in Chemistry at the University of California, Berkeley, and did his post-doctoral research in cell biology at the University of California, San Francisco.