Humoral and cellular responses to mRNA vaccines against SARS-CoV-2 in patients with a history of CD20 B-cell-depleting therapy (RituxiVac): an investigator-initiated, single-centre, open-label study.

Autor:	Moor MB; Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Department of Biomedical Research, University of Bern, Bern, Switzerland., Suter-Riniker F; Institute for Infectious Diseases, University of Bern, Bern, Switzerland., Horn MP; Department of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Aeberli D; Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Department of Biomedical Research, University of Bern, Bern, Switzerland., Amsler J; Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Department of Biomedical Research, University of Bern, Bern, Switzerland., Möller B; Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Department of Biomedical Research, University of Bern, Bern, Switzerland., Njue LM; Department of Haematology and Central Haematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Medri C; Department of Haematology and Central Haematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Angelillo-Scherrer A; Department of Haematology and Central Haematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Borradori L; Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Radonjic-Hoesli S; Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Seyed Jafari SM; Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Chan A; Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Hoepner R; Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Bacher VU; Department of Haematology and Central Haematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Mani LY; Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Department of Biomedical Research, University of Bern, Bern, Switzerland., Iype JM; Department of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Hirzel C; Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Maurer B; Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Department of Biomedical Research, University of Bern, Bern, Switzerland., Sidler D; Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Department of Biomedical Research, University of Bern, Bern, Switzerland.
Jazyk:	angličtina
Zdroj:	The Lancet. Rheumatology [Lancet Rheumatol] 2021 Nov; Vol. 3 (11), pp. e789-e797. Date of Electronic Publication: 2021 Sep 07.
DOI:	10.1016/S2665-9913(21)00251-4
Abstrakt:	Background: B-cell-depleting therapies increase the risk of morbidity and mortality due to COVID-19. Evidence-based SARS-CoV-2 vaccination strategies for patients on B-cell-depleting therapies are scarce. We aimed to investigate humoral and cell-mediated immune responses to SARS-CoV-2 mRNA-based vaccines in patients receiving CD20-targeted B-cell-depleting agents for autoimmune disease, malignancy, or transplantation. Methods: The RituxiVac study was an investigator-initiated, single-centre, open-label study done at the Bern University Hospital (Bern, Switzerland). Patients with a treatment history of anti-CD20-depleting agents (rituximab or ocrelizumab) and with no previous history of SARS-CoV-2 infection were enrolled between April 26 and June 30, 2021, for analysis of humoral and cell-mediated immune responses (by interferon-γ [IFNγ] release assay) at least 4 weeks after completing vaccination against SARS-CoV-2. Healthy controls without a history of SARS-CoV-2 infection were also enrolled at least 4 weeks after completing vaccination against SARS-CoV-2. All study participants received two doses of either the Pfizer-BioNTech BNT162b2 vaccine or the Moderna mRNA-1273 vaccine. The primary outcome was the proportion of patients with a history of anti-CD20 treatment who showed a humoral immune response against the SARS-CoV-2 spike protein in comparison with immunocompetent controls. Prespecified secondary endpoints were the effect of anti-CD20 therapy (including time since last treatment and cumulative dose) on humoral or cell-mediated immune responses to SARS-CoV-2 vaccination, and biomarkers of immunocompetence. This study is registered with ClinicalTrials.gov, NCT04877496. Findings: The final study population comprised 96 patients and 29 immunocompetent controls. The median age of patients was 67 years (IQR 57-72) and of controls was 54 years (45-62), and 51 (53%) of 96 patients and 19 (66%) of 29 controls were female. The median time since last anti-CD20 treatment was 1·07 years (IQR 0·48-2·55) and the median cumulative dose of an anti-CD20 depleting agent was 2·80 g (1·50-5·00). Anti-spike IgG antibodies were detected in 47 (49%) of 96 patients 1·79 months (IQR 1·16-2·48) after the second vaccine dose compared to 29 (100%) of 29 controls 1·81 months (1·17-2·48) after the second vaccine dose (p<0·001). SARS-CoV-2-specific IFNγ release was detected in 13 (20%) of 66 patients and 21 (75%) of 28 of healthy controls (p<0·001). Only nine (14%) of 66 patients were double positive for anti-SARS-CoV-2 spike IgG and cell-mediated responses, compared with 21 (75%) of 28 healthy controls (p<0·001). Time since last anti-CD20 therapy (>7·6 months; positive predictive value 0·78), peripheral CD19 + cell count (>27 cells per μL; positive predictive value 0·70), and CD4 + lymphocyte count (>653 cells per μL; positive predictive value 0·71) were predictive of humoral vaccine response (area under the curve [AUC] 67% [95% CI 56-78] for time since last anti-CD20 therapy, 67% [55-80] for peripheral CD19 + count, and 66% [54-79] for CD4 + count). Interpretation: This study provides further evidence of blunted humoral and cell-mediated immune responses elicited by SARS-CoV-2 mRNA vaccines in patients with a history of CD20 B-cell-depleting treatment. Lymphocyte subpopulation counts were associated with vaccine response in this highly vulnerable population. On validation, these results could help guide both the administration of SARS-CoV-2 vaccines and B-cell-depleting agents in this population. Funding: Bern University Hospital. Competing Interests: We declare no competing interests. (© 2021 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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