Timing of SARS-CoV-2 Vaccination Matters in People With Multiple Sclerosis on Pulsed Anti-CD20 Treatment.


Journal

Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388

Informations de publication

Date de publication:
11 2022
Historique:
received: 23 12 2021
accepted: 01 08 2022
entrez: 12 10 2022
pubmed: 13 10 2022
medline: 15 10 2022
Statut: epublish

Résumé

Our objective was to investigate cellular and humoral immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in a cohort of people with multiple sclerosis (pwMS) on pulsed B-cell-depleting treatment (BCDT). In particular, we intended to evaluate a possible association between immune responses and the timing of vaccination under BCDT. We conducted a cross-sectional study among pwMS on pulsed BCDT or without disease-modifying treatment after completed SARS-CoV-2 vaccination. Samples were collected during routine clinical visits at the Multiple Sclerosis Center Dresden, Germany, between June 2021 and September 2021. Blood was analyzed for SARS-CoV-2 spike protein-specific antibodies and interferon-γ release of CD4 and CD8 T cells on stimulation with spike protein peptide pools. Lymphocyte subpopulations and total immunoglobulin levels in the blood were measured as part of clinical routine. We included 160 pwMS in our analysis, comprising 133 pwMS on BCDT (n = 132 on ocrelizumab and n = 1 on rituximab) and 27 without disease-modifying treatment. Humoral and cellular anti-SARS-CoV-2 responses were reciprocally regulated by the time between the last BCDT cycle and vaccination. Although antibody responses increased with prolonged intervals between the last BCDT cycle and vaccination, CD4 and CD8 T-cell responses were higher in pwMS vaccinated at early time points after the last BCDT cycle compared with untreated pwMS. T-cellular vaccination responses correlated with total, CD3 CD4, and partly with CD3 CD8 lymphocyte counts. Humoral responses correlated with CD19 lymphocyte counts. Status post coronavirus disease 2019 infection led to significantly increased SARS-CoV-2-specific T-cell and antibody responses. Delaying BCDT is currently discussed as a strategy to optimize humoral responses to SARS-CoV-2 vaccination. However, T cells represent an important line of defense against SARS-CoV-2 infection as well, especially in light of emerging variants of concern. We observed enhanced CD4 and CD8 T-cellular responses in pwMS receiving vaccination at early time points after their last BCDT cycle. These data may influence clinical decision making with respect to vaccination strategies in patients receiving BCDT.

Sections du résumé

BACKGROUND AND OBJECTIVES
Our objective was to investigate cellular and humoral immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in a cohort of people with multiple sclerosis (pwMS) on pulsed B-cell-depleting treatment (BCDT). In particular, we intended to evaluate a possible association between immune responses and the timing of vaccination under BCDT.
METHODS
We conducted a cross-sectional study among pwMS on pulsed BCDT or without disease-modifying treatment after completed SARS-CoV-2 vaccination. Samples were collected during routine clinical visits at the Multiple Sclerosis Center Dresden, Germany, between June 2021 and September 2021. Blood was analyzed for SARS-CoV-2 spike protein-specific antibodies and interferon-γ release of CD4 and CD8 T cells on stimulation with spike protein peptide pools. Lymphocyte subpopulations and total immunoglobulin levels in the blood were measured as part of clinical routine.
RESULTS
We included 160 pwMS in our analysis, comprising 133 pwMS on BCDT (n = 132 on ocrelizumab and n = 1 on rituximab) and 27 without disease-modifying treatment. Humoral and cellular anti-SARS-CoV-2 responses were reciprocally regulated by the time between the last BCDT cycle and vaccination. Although antibody responses increased with prolonged intervals between the last BCDT cycle and vaccination, CD4 and CD8 T-cell responses were higher in pwMS vaccinated at early time points after the last BCDT cycle compared with untreated pwMS. T-cellular vaccination responses correlated with total, CD3 CD4, and partly with CD3 CD8 lymphocyte counts. Humoral responses correlated with CD19 lymphocyte counts. Status post coronavirus disease 2019 infection led to significantly increased SARS-CoV-2-specific T-cell and antibody responses.
DISCUSSION
Delaying BCDT is currently discussed as a strategy to optimize humoral responses to SARS-CoV-2 vaccination. However, T cells represent an important line of defense against SARS-CoV-2 infection as well, especially in light of emerging variants of concern. We observed enhanced CD4 and CD8 T-cellular responses in pwMS receiving vaccination at early time points after their last BCDT cycle. These data may influence clinical decision making with respect to vaccination strategies in patients receiving BCDT.

Identifiants

pubmed: 36224045
pii: 9/6/e200031
doi: 10.1212/NXI.0000000000200031
pmc: PMC9558629
pii:
doi:

Substances chimiques

Antigens, CD20 0
COVID-19 Vaccines 0
Spike Glycoprotein, Coronavirus 0
spike protein, SARS-CoV-2 0
Rituximab 4F4X42SYQ6
Interferon-gamma 82115-62-6

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Christina Woopen (C)

From the Center of Clinical Neuroscience (C.W., M.D., R.H., K.A., T.Z.), Department of Neurology, University Hospital Carl Gustav Carus Dresden, Technical University of Dresden, Germany; and F. Hoffmann-La Roche Ltd. (C.R., R.P.), Basel, Switzerland.

Marie Dunsche (M)

From the Center of Clinical Neuroscience (C.W., M.D., R.H., K.A., T.Z.), Department of Neurology, University Hospital Carl Gustav Carus Dresden, Technical University of Dresden, Germany; and F. Hoffmann-La Roche Ltd. (C.R., R.P.), Basel, Switzerland.

Rocco Haase (R)

From the Center of Clinical Neuroscience (C.W., M.D., R.H., K.A., T.Z.), Department of Neurology, University Hospital Carl Gustav Carus Dresden, Technical University of Dresden, Germany; and F. Hoffmann-La Roche Ltd. (C.R., R.P.), Basel, Switzerland.

Catarina Raposo (C)

From the Center of Clinical Neuroscience (C.W., M.D., R.H., K.A., T.Z.), Department of Neurology, University Hospital Carl Gustav Carus Dresden, Technical University of Dresden, Germany; and F. Hoffmann-La Roche Ltd. (C.R., R.P.), Basel, Switzerland.

Rosetta Pedotti (R)

From the Center of Clinical Neuroscience (C.W., M.D., R.H., K.A., T.Z.), Department of Neurology, University Hospital Carl Gustav Carus Dresden, Technical University of Dresden, Germany; and F. Hoffmann-La Roche Ltd. (C.R., R.P.), Basel, Switzerland.

Katja Akgün (K)

From the Center of Clinical Neuroscience (C.W., M.D., R.H., K.A., T.Z.), Department of Neurology, University Hospital Carl Gustav Carus Dresden, Technical University of Dresden, Germany; and F. Hoffmann-La Roche Ltd. (C.R., R.P.), Basel, Switzerland.

Tjalf Ziemssen (T)

From the Center of Clinical Neuroscience (C.W., M.D., R.H., K.A., T.Z.), Department of Neurology, University Hospital Carl Gustav Carus Dresden, Technical University of Dresden, Germany; and F. Hoffmann-La Roche Ltd. (C.R., R.P.), Basel, Switzerland. tjalf.ziemssen@uniklinikum-dresden.de.

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Classifications MeSH