Authors
Curtin, R., Velmurugu, Y., Dibba, F., Hao, Y., Sreenivasaiah, C., Khodadadi-Jamayran, A., Nyovanie, S. T., Kim, A., Samanovic-Golden, M., Mulligan, M. J., Priest, J., Cabatingan, M., Winger, R., Patskovsky, Y., Kister, I., Silverman, G. J., Krogsgaard, M.
Abstract
Patients with multiple sclerosis (pwMS) treated with ocrelizumab (OCR), a B-cell-depleting therapy, exhibit heterogeneous humoral responses to SARS-CoV-2 mRNA vaccination. The mechanisms underlying this heterogeneity remain poorly understood. We performed a longitudinal analysis of antigen-specific T and B cell responses in OCR-treated pwMS and non-MS healthy controls following vaccination. Based on post-vaccination anti-Spike IgG titers, pwMS were categorized as super-responders (SR), responders (R), or non-responders (NR). We investigated how immune cell composition, timing of OCR infusion, and lymphocyte subset dynamics influenced humoral response outcomes. While CD4+ and CD8+ T cell populations were largely preserved across all OCR-treated pwMS, distinct differences in the representation of residual B cell composition distinguished responders from non-responders. Notably, CD19+CD27+ classical memory B cells and CD19+CD27-IgD-T-bet+CD11c+CXCR5- DN2-like B cells persisted following OCR infusion and were enriched in the SR group compared to the NR group. Our findings identify persistent memory B cell subsets that escape OCR depletion as key immune correlates and mechanistic mediators of vaccine responsiveness in OCR-treated pwMS, highlighting potential targets to enhance vaccine efficacy in this population. All participating patients were enrolled in clinical trials NCT04843774 and NCT04682548.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 05 Nov 2025.
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