Distinct Patterns of Humoral and Cellular Immune Responses Following SARS-CoV-2 mRNA Vaccination in Patients With Immune-Mediated Neurological Disorders on Anti-CD20 Therapy: A Prospective Cohort Study

Background: Patients with neuroimmunological disorders on anti-CD20 therapy are at increased risk of severe COVID-19. However, little is known about SARS-CoV-2 vaccine efficacy in this cohort. In particular, the impact of B cell depletion on humoral and cellular immune responses to SARS-CoV-2 vaccination remains poorly defined. No study has addressed vaccine responses to the SARS-CoV-2 delta variant in immunocompromised individuals so far. Methods: In this prospective cohort study we investigated humoral and cellular responses in serial samples from 164 individuals after SARS-CoV-2 mRNA vaccination (82 patients with neuroimmunological disorders on anti-CD20 therapy and 82 healthy controls). Antibodies were quantified using the Elecsys anti-SARS-CoV-2 S immunoassay against the receptor-binding (RBD) domain. T cell responses against the SARS-CoV-2 Wuhan strain and the delta variant were assessed by IFN-g enzyme-linked immunosorbent spot assays.  Findings: Following vaccination, SARS-CoV-2 –specific antibodies were detected in 57/82 (70%) patients compared to 82/82 (100%) healthy controls (p<0·001). Seroconversion rates and antibody levels were lower in B cell-depleted (<1 B cell/mcl) patients compared to non-depleted (≥ 1 B cell/mcl) patients (p<0·001). B cell levels ≥ 1 cell/mcl were sufficient to induce anti-SARS-CoV-2-S antibody responses. In contrast to the antibody response, most B cell-depleted patients generated a T-cell response against the SARS-CoV-2 Wuhan strain and the delta variant that was more robust in frequency (p<0·05) and magnitude (p<0·01) compared to non-depleted patients and persisted for at least six weeks. Interpretation: Humoral immunity following SARS-CoV-2 mRNA vaccination can be achieved in patients on anti-CD20 therapy once B cells start to repopulate. In the absence of B cells, a robust and stable T cell response is generated which may provide a potent defense against severe COVID-19 in this high-risk patient population.  Funding Information: Funded partly by a Medical-Scientific fund of the Major of the federal capital of Vienna (grant Covid003). Declaration of Interests: BK has received honoraria for speaking and for consulting from Biogen, BMS-Celgene, JohnsonJ Schering, Teva-Ratiopharm. There are no conflicts of interest with respect to the present study, PR has received honoraria for speaking and for consulting from Alexion, Almirall, Amicus, Biogen, Merck, Novartis, Roche, Teva, Sandoz, and Sanofi Genzyme outside of the submitted work. He has received research grants from Amicus, Biogen, Merck and Roche outside the submitted work. GZ recieved speaking honoria from biogen and has participated in meetings sponsored by or received travel funding from Biogen, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. No conflict of interest regarding this study, GB has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, Celgene/BMS, Lilly, Merck, Novartis, Roche, Sanofi-Genzyme and Teva, and received honoraria for consulting Biogen, Celgene/BMS, Novartis, Roche, Sanofi-Genzyme and Teva. He has received financial support in the past 12 months by unrestricted research grants (Celgene/BMS, Novartis). No conflict of interest with respect to the present study, ADB declares no conflict of interest related to the content of this article. Independent of this study, ADB has participated in meetings sponsored by or received speaker honoraria or travel funding from Biogen, Merck, Novartis, Roche, Celgene (BMS), and Sanofi. She has received an unrestricted grant from Merck GmbH, an affiliate of Merck KGaA and is currently supported by a research grant from Biogen. TB has no particular conflicts of interest regarding the present study. In general, he has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) from pharmaceutical companies marketing treatments for multiple sclerosis: Almirall, Bayer, Biogen, Biologix, Bionorica, Genzyme, GSK, Janssen-Cilag, MedDay, Merck, Novartis, Octapharma, Roche, Sanofi/Genzyme, TG Pharmaceuticals, TEVAratiopharm and UCB. His institution has received financial support in the last 12 months by unrestricted research grants (Biogen, Bayer, Merck, Novartis, Sanofi/Genzyme, and TEVA ratiopharm) and for participation in clinical trials in multiple sclerosis sponsored by Alexion, Bayer, Biogen, Merck, Novartis, Octapharma, Roche, Sanofi/Genzyme, and TEVA. LS, HH, RT, FZ, WR, KZ, IW, AS, MG, MM, KR, SW, JHA, ST report no conflicts of interest. Ethics Approval Statement: Subjects gave written informed consent. The study was approved by the ethics committee of the Medical University of Vienna, Austria, EK Nr. 1073/2021.