Longitudinal study of immunity to SARS-CoV2 in Ocrelizumab-treated multiple sclerosis patients up to 2 years after COVID-19 vaccination
ABSTRACT Objectives 1 To plot the trajectory of humoral and cellular immune responses to the primary (two-dose) COVID-19 mRNA series and the third/booster dose in B-cell-depleted multiple sclerosis (MS) patients up to 2 years post-vaccination; 2. to identify predictors of immune responses to vaccination; and 3. to assess the impact of intercurrent COVID-19 infections on SARS CoV-2-specific immunity.Methods 60 Ocrelizumab-treated MS patients were enrolled from NYU (New York) and University of Colorado (Anschutz) MS Centers. Samples were collected pre-vaccination, and then 4, 12, 24, and 48 weeks post-primary series, and 4, 12, 24, and 48 weeks post-booster. Binding anti-Spike antibody responses were assessed with multiplex bead-based immunoassay (MBI) and electrochemiluminescence (Elecsys®, Roche Diagnostics), and neutralizing antibody responses with live-virus immunofluorescence-based microneutralization assay. Spike-specific cellular responses were assessed with IFNγ/IL-2 ELISpot (Invitrogen) and, in a subset, by sequencing complementary determining regions (CDR)-3 within T-cell receptors (Adaptive Biotechnologies). A linear mixed effect model was used to compare antibody and cytokine levels across time points. Multivariate analyses identified predictors of immune responses.Results The primary vaccination induced an 11-208-fold increase in binding and neutralizing antibody levels and a 3-4-fold increase in IFNγ/IL-2 responses, followed by a modest decline in antibody but not cytokine responses. Booster dose induced a further 3-5-fold increase in binding antibodies and 4-5-fold increase in IFNγ/IL-2, which were maintained for up to 1 year. Infections had a variable impact on immunity.Interpretation Humoral and cellular benefits of COVID-19 vaccination in B-cell-depleted MS patients were sustained for up to 2 years when booster doses were administered..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 27. Jan. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kister, Ilya [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2024.01.23.24301671 |
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| PPN (Katalog-ID): |
XBI042286654 |
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| 520 | |a ABSTRACT Objectives 1 To plot the trajectory of humoral and cellular immune responses to the primary (two-dose) COVID-19 mRNA series and the third/booster dose in B-cell-depleted multiple sclerosis (MS) patients up to 2 years post-vaccination; 2. to identify predictors of immune responses to vaccination; and 3. to assess the impact of intercurrent COVID-19 infections on SARS CoV-2-specific immunity.Methods 60 Ocrelizumab-treated MS patients were enrolled from NYU (New York) and University of Colorado (Anschutz) MS Centers. Samples were collected pre-vaccination, and then 4, 12, 24, and 48 weeks post-primary series, and 4, 12, 24, and 48 weeks post-booster. Binding anti-Spike antibody responses were assessed with multiplex bead-based immunoassay (MBI) and electrochemiluminescence (Elecsys®, Roche Diagnostics), and neutralizing antibody responses with live-virus immunofluorescence-based microneutralization assay. Spike-specific cellular responses were assessed with IFNγ/IL-2 ELISpot (Invitrogen) and, in a subset, by sequencing complementary determining regions (CDR)-3 within T-cell receptors (Adaptive Biotechnologies). A linear mixed effect model was used to compare antibody and cytokine levels across time points. Multivariate analyses identified predictors of immune responses.Results The primary vaccination induced an 11-208-fold increase in binding and neutralizing antibody levels and a 3-4-fold increase in IFNγ/IL-2 responses, followed by a modest decline in antibody but not cytokine responses. Booster dose induced a further 3-5-fold increase in binding antibodies and 4-5-fold increase in IFNγ/IL-2, which were maintained for up to 1 year. Infections had a variable impact on immunity.Interpretation Humoral and cellular benefits of COVID-19 vaccination in B-cell-depleted MS patients were sustained for up to 2 years when booster doses were administered. | ||
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| 700 | 1 | |a Piquet, Amanda L. |4 aut | |
| 700 | 1 | |a Borko, Tyler |4 aut | |
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| 700 | 1 | |a Bacon, Tamar E. |4 aut | |
| 700 | 1 | |a Kim, Angie |4 aut | |
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| 700 | 1 | |a Nyovanie, Samantha |4 aut | |
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| 700 | 1 | |a Samanovic, Marie I. |4 aut | |
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| 700 | 1 | |a Krogsgaard, Michelle |4 aut | |
| 700 | 1 | |a Silverman, Gregg J. |4 aut | |
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