Impact of pre-existing immunity on clonal evolution and diversification of memory B cells in response to H2 influenza vaccination

Authors

• AB Spangler
• R Malek
• GD Shimberg
• GE Mantus
• LY Cominsky
• JE Raab
• SR Gajjala
• KV Houser
• SF Andrews

Abstract

It has been well documented that pre-existing immunity affects vaccine responses. Here, we investigate how pre-existing immunity impacts the clonal evolution and diversification of the memory B cell receptor (BCR) repertoire upon vaccination. We sampled peripheral blood B cells from individuals vaccinated with an H2 HA ferritin nanoparticle vaccine that were either naïve to H2N2 at the time of vaccination or previously exposed to H2N2 influenza virus fifty years ago. Single-cell whole transcriptome, cell surface protein and B cell receptor data (BCR) was generated for H2-specific memory B cells collected between 0 and 40 weeks after vaccination. To study BCR clonal evolution and diversity, we used Immcantation bioinformatic tools to identify BCR lineages and construct phylogenetic trees of longitudinally sampled clones to determine whether these lineages were significantly evolving over time. We found that 52% of H2 specific BCR lineages were evolving in H2 naïve individuals compared to less than 10% of lineages from H2 exposed individuals. We further analyzed lineage evolution and clonal relationships across different phenotypic memory B cell subsets to study precursor-progeny relationships. We observed close interconnectedness between the different memory populations in both H2 naïve and H2 exposed individuals. All together, we conclude that the BCR repertoire undergoes little change upon vaccination in individuals with pre-existing immunity.

Scientific Focus Area: Immunology

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