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Apostolidis, Sokratis A; Kakara, Mihir; Painter, Mark M; Goel, Rishi R; Mathew, Divij; Lenzi, Kerry; Rezk, Ayman; Patterson, Kristina R; Espinoza, Diego A; Kadri, Jessy C; Markowitz, Daniel M; E Markowitz, Clyde; Mexhitaj, Ina; Jacobs, Dina; Babb, Allison; Betts, Michael R; Prak, Eline T Luning; Weiskopf, Daniela; Grifoni, Alba; Lundgreen, Kendall A; Gouma, Sigrid; Sette, Alessandro; Bates, Paul; Hensley, Scott E; Greenplate, Allison R; Wherry, E John; Li, Rui; Bar-Or, Amit
Nature medicine, 11/2021, Letnik: 27, Številka: 11Journal Article
SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (T ) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (T 1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating T responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20.
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in: SICRIS
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