PhD Candidate Yale University New Haven, Connecticut, United States
Disclosure(s):
Burhan Sabuwala, M Tech: No financial relationships to disclose
Introduction/Rationale: Vaccine responses vary across individuals, with specific B cell subpopulations driving humoral immune response. Bulk transcriptomic studies have identified pan-vaccine predictive signatures, but have difficulty determining which cell subsets drive these signals. Single-cell approaches offer the cellular resolution to link signatures to specific subpopulations, and recent study have successfully associated B cell subsets with vaccine responsiveness. However, most single-cell vaccine studies use small cohorts ( < 10 subjects) with insufficient power to reliably detect rare cell states like functionally distinct plasma cell subsets and subtypes of memory B cells. Moreover, inconsistent cell annotations hinder cross-study comparisons. A large-scale, standardized B cell atlas across multiple vaccines would facilitate detection of rare response-associated populations and establish reference subset definitions.
Methods: We curated and processed nine single-cell RNA-seq studies (53 subjects) following SARS-CoV-2, seasonal influenza, and malaria vaccinations spanning baseline through various timepoints post-vaccination. All datasets were processed through a standardized pipeline and integrated to preserve biological variation while correcting technical batch effects. Hierarchical celltype annotation was applied to identify B cell subpopulations.
Results: The integrated atlas comprises 447,493 B cells spanning naïve (50-70%), memory (25-40%), activated, and plasma cell populations in PBMC samples across three different vaccine responses. We observe plasmablast enrichment post-vaccination consistent with peak antibody responses across many vaccines.
Conclusion: This multi-vaccine B cell atlas enables systematic profiling of rare response-associated subpopulations not detectable in small-cohort studies. Integration of transcriptional states with antibody outcomes may reveal cellular predictors of immune response.
