B-Cell Subset Representation Predicts SARS-CoV-2 Vaccine Response in Solid Organ Transplant Recipients.

Abstract

Solid organ transplant recipients (SOTRs) suffer increased morbidity and mortality due, in part, to chronic immunosuppression. The determination of an individual's immune competence is currently difficult but would improve risk assessment and inform medical decisions. We reasoned that correlating qualitative and quantitative measures of the B-cell compartment with serologic responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination would reveal novel B-cell-based predictors of immune competence. We performed an integrated analysis of B-cell phenotypes, serology, and antibody repertoires in heart, lung, liver, kidney, and multiorgan transplant recipients and healthcare worker (HCW) controls (62 individuals total). We utilized K-means clustering and correlation analyses to identify B-cell features that correlated with vaccine serology. K-means clustering identified 3 distinct B-cell compartment-based groups in SOTRs, which correlated with serum responses to SARS-CoV-2 vaccination. Group 1 SOTRs had a naive-dominant circulating B-cell pool and serologic responses closest to HCWs. Group 2 SOTRs had reduced naive but hyperexpanded memory B cells (MBCs) and variable vaccine responses that segregated by immunosuppression. Group 3 SOTRs had lymphopenia across B-cell subsets and poor serologic responses. Antibody repertoire analysis showed reduced clonal diversity across SOTRs, regardless of MBC numbers. Even in SOTRs with the largest immune responses, vaccine-specific B cells showed evidence of reduced maturation and clonal diversity. These findings reveal a hierarchy of B-cell impairment in SOTRs that can be measured rapidly, with implications for immune monitoring and intervention in immunocompromised individuals.