Analysis of B Cell Repertoire Dynamics Following Hepatitis B Vaccination in Humans, and Enrichment of Vaccine-specific Antibody Sequences

• There is B cell immunoglobulin sequence expansion and mutation 7 days after vaccination.
• There is sequence convergence between participants 14 and 21 days after vaccination with a common antigen.
• These properties allow de novo identification of vaccine-specific immunoglobulin sequence clusters.The B cell repertoire is a diverse system that adapts in response to infection/vaccination to protect against disease. Next-generation sequencing can be used to study this system at the level of the B cell immunoglobulin sequences, but it is difficult to distinguish the sequences responding to the antigen of interest from background noise. By sequencing both the total and vaccine-specific B cell immunoglobulin repertoire, we show that there are time-limited perturbations in the total repertoire following vaccination. These data were used to develop models for the enrichment of vaccine-specific sequences, which could give insight into the underlying biology of vaccination.

Generating a diverse B cell immunoglobulin repertoire is essential for protection against infection. The repertoire in humans can now be comprehensively measured by high-throughput sequencing. Using hepatitis B vaccination as a model, we determined how the total immunoglobulin sequence repertoire changes following antigen exposure in humans, and compared this to sequences from vaccine-specific sorted cells. Clonal sequence expansions were seen 7 days after vaccination, which correlated with vaccine-specific plasma cell numbers. These expansions caused an increase in mutation, and a decrease in diversity and complementarity-determining region 3 sequence length in the repertoire. We also saw an increase in sequence convergence between participants 14 and 21 days after vaccination, coinciding with an increase of vaccine-specific memory cells. These features allowed development of a model for in silico enrichment of vaccine-specific sequences from the total repertoire. Identifying antigen-specific sequences from total repertoire data could aid our understanding B cell driven immunity, and be used for disease diagnostics and vaccine evaluation.