BAFF-R Expression as a Predictive Biomarker for COVID-19 Vaccine Non-Responsiveness in Antibody-Deficient Patients

Patients with primary and secondary antibody deficiencies exhibit variable responses to vaccination, with a substantial proportion failing to mount protective immunity to SARS-CoV-2. Mechanisms underpinning vaccine non-responsiveness in this population remain poorly defined. Our objective was to investigate B-cell-intrinsic defects underlying SARS-CoV-2 vaccine failure by assessing the capacity for plasma cell differentiation in a heterogeneous cohort of antibody-deficient patients using an in vitro model. Overall design: Peripheral B-cells from 50 patients enrolled in the COVID-19 in Antibody Deficiency (COV-AD) study underwent a validated in vitro B-cell differentiation assay. We assessed plasmablast and plasma cell generation, immunoglobulin production, B-cell receptor repertoire diversity, and BAFF-R surface expression. RNA sequencing was performed on pre-activated B-cells to evaluate BAFF-R encoding gene, TNFRSF13C and related gene expression.