1. Longitudinal study of immunity to SARS-CoV2 in ocrelizumab-treated MS patients up to 2 years after COVID-19 vaccination.
- Author
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Kister I, Curtin R, Piquet AL, Borko T, Pei J, Banbury BL, Bacon TE, Kim A, Tuen M, Velmurugu Y, Nyovanie S, Selva S, Samanovic MI, Mulligan MJ, Patskovsky Y, Priest J, Cabatingan M, Winger RC, Krogsgaard M, and Silverman GJ
- Subjects
- Humans, Male, Female, Middle Aged, Adult, Longitudinal Studies, Antibodies, Viral blood, Antibodies, Neutralizing blood, Antibodies, Neutralizing immunology, Immunity, Cellular drug effects, Vaccination, Immunity, Humoral drug effects, Immunity, Humoral immunology, BNT162 Vaccine administration & dosage, BNT162 Vaccine immunology, COVID-19 immunology, COVID-19 prevention & control, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized pharmacology, Antibodies, Monoclonal, Humanized administration & dosage, COVID-19 Vaccines immunology, COVID-19 Vaccines administration & dosage, SARS-CoV-2 immunology, Multiple Sclerosis immunology, Multiple Sclerosis drug therapy
- 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: Sixty 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 complementarity 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- to 208-fold increase in binding and neutralizing antibody levels and a 3- to 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- to 5-fold increase in binding antibodies and 4- to 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., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
- Published
- 2024
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