Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6087409 | Clinical Immunology | 2014 | 11 Pages |
â¢Deep-sequencing of plasmablast antibody repertoires to influenza vaccinationâ¢Single-cell barcoding enables recovery of natively paired heavy- and light-chains.â¢Identification of clonal families of antibodies with shared rearrangementsâ¢Antibodies from clonal populations are enriched for binding and neutralization.â¢Some antibodies induced by influenza vaccination exhibit original antigenic sin.
We developed a DNA barcoding method to enable high-throughput sequencing of the cognate heavy- and light-chain pairs of the antibodies expressed by individual B cells. We used this approach to elucidate the plasmablast antibody response to influenza vaccination. We show that >Â 75% of the rationally selected plasmablast antibodies bind and neutralize influenza, and that antibodies from clonal families, defined by sharing both heavy-chain VJ and light-chain VJ sequence usage, do so most effectively. Vaccine-induced heavy-chain VJ regions contained on average >Â 20 nucleotide mutations as compared to their predicted germline gene sequences, and some vaccine-induced antibodies exhibited higher binding affinities for hemagglutinins derived from prior years' seasonal influenza as compared to their affinities for the immunization strains. Our results show that influenza vaccination induces the recall of memory B cells that express antibodies that previously underwent affinity maturation against prior years' seasonal influenza, suggesting that 'original antigenic sin' shapes the antibody response to influenza vaccination.