High Throughput Sequencing of the Human Antibody Repertoire in Response to Influenza Vaccination (58.14)

Abstract

Despite the many advances in personal genome analysis, the immunoglobulin repertoire of the genome, while central to human health, is in practice extraordinarily challenging to measure and analyze. There are several reasons for this, including the facts that each B cell contains a distinct antibody sequence encoded in its genome, that the antibody repertoire is not constant but changes over time, and the high similarity between antibody sequences. We have addressed this challenge by using high-throughput long read sequencing to perform immunogenetic characterization of expressed human antibody repertoires. Informatic analysis of large numbers of antibody heavy chain sequences from individual subjects allowed us to perform global characterizations of isotype distributions, clonal lineage structure of the repertoire and age-related mutational activity. With influenza vaccination as a specific stimulus, we used lineage analysis to measure the clonal structure and mutational distribution of individuals’ repertoires; analysis of this data showed that elderly subjects have a decreased number of lineages but an increased pre-vaccination mutation load in their repertoire and that some of these subjects have an oligoclonal character to their repertoire in which the diversity of the lineages is greatly reduced relative to younger subjects. These analyses may ultimately be useful as metrics to measure vaccine response and to further understand impaired immune function in aging.