To identify sources of inter-subject variation in vaccine responses, we performed high-frequency sampling of human peripheral blood cells post-vaccination, followed by a novel systems biology analysis. Functional principal component analysis was used to examine time varying B cell vaccine responses. In subjects vaccinated within the previous three years, 90% of transcriptome variation was explained by a single subject-specific mathematical pattern. Within individual vaccine response patterns, a common subset of 742 genes was strongly correlated with migrating plasma cells. Of these, 366 genes were associated with human plasmablasts differentiating in vitro. Additionally, subject-specific temporal transcriptome patterns in peripheral blood mononuclear cells identified migration of myeloid/dendritic cell lineage cells one day after vaccination. Upstream analyses of transcriptome changes suggested both shared and subject-specific transcription groups underlying larger patterns. With robust statistical methods, time-varying response characteristics of individual subjects were effectively captured along with a shared plasma cell gene signature.